Trial Outcomes & Findings for Oral Topotecan to Treat Recurrent or Persistent Solid Tumors (NCT NCT00382733)

Last Updated: 2013-07-22

Results Overview

The MTD of metronomic oral topotecan was determined using a standard 3+3 dose escalation cohort design. The total sample and the number of subjects who receive each dose in this design depends on the frequency of dose limiting toxicities (DLTs)at each dose level. If 0 out of 3 subjects experience a DLT at a given dose level, 3 subjects will be enrolled at the next higher dose level. If greater than or equal to 2 subjects experience a DLT at a given dose level, dose escalation will be stopped. If 1 out of 3 subjects experience a DLT at a given dose level, 3 subjects are enrolled at the same dose level.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

26 participants

Primary outcome timeframe

MTD was assessed during the first cycle of treatment (days 1-28).

Results posted on

2013-07-22

Participant Flow

The study was open to enrollment at one community oncology clinic from November 2006 to May 2009.

Informed consent was obtained from all subjects. All subjects underwent a screening period that could last up to 4 weeks during which pre-study assessments were completed. During the dose finding portion of the study, subjects were assigned to a Dose Level during enrollment. Once the MTD was determined, additional subjects were treated at the MTD.

Participant milestones

Participant milestones
Measure	Oral Topotecan 0.25 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1).	Oral Topotecan 0.50 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	Oral Topotecan 0.75 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	Oral Topotecan 1.0 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	Oral Topotecan 1.25 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Overall Study STARTED	3	4	3	14	2
Overall Study COMPLETED	3	3	3	14	2
Overall Study NOT COMPLETED	0	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Oral Topotecan 0.25 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1).	Oral Topotecan 0.50 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	Oral Topotecan 0.75 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	Oral Topotecan 1.0 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	Oral Topotecan 1.25 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Overall Study Withdrawal by Subject	0	1	0	0	0

Baseline Characteristics

Oral Topotecan to Treat Recurrent or Persistent Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metronomic Oral Topotecan n=26 Participants All subjects received metronomic oral topotecan daily at the assigned dose level.
Age Continuous	65.6 years STANDARD_DEVIATION 8.99 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants

PRIMARY outcome

Timeframe: MTD was assessed during the first cycle of treatment (days 1-28).

Population: DLT information was available for 3 subjects who received a topotecan dose of 0.25 mg/day, 3 subjects who received a topotecan dose of 0.50 mg/day, 3 subjects who received a topotecan dose of 0.75 mg/day, 3 subjects who received a topotecan dose of 1.0 mg/day, and 2 subjects who received a topotecan dose of 1.25 mg/day.

Outcome measures

Outcome measures
Measure	Metronomic Oral Topotecan n=14 Participants All subjects received metronomic oral topotecan daily at the assigned dose level.	Oral Topotecan 0.50 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	Oral Topotecan 0.75 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	Oral Topotecan 1.0 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	Oral Topotecan 1.25 mg Daily All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Maximum Tolerated Dose (MTD) of Single Agent Metronomic Oral Topotecan	1.0 mg/day	—	—	—	—

SECONDARY outcome

Timeframe: DLTs were assessed during the first cycle of treatment (days 1-28).

Population: Number of participants analyzed refers to those for whom DLT information was available during the dose finding portion of the study.

DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. This measure reports the number of subjects who experienced DLT at each dose level during the dose finding portion of the study.

Outcome measures

Outcome measures
Measure	Metronomic Oral Topotecan n=3 Participants All subjects received metronomic oral topotecan daily at the assigned dose level.	Oral Topotecan 0.50 mg Daily n=3 Participants All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	Oral Topotecan 0.75 mg Daily n=3 Participants All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	Oral Topotecan 1.0 mg Daily n=3 Participants All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	Oral Topotecan 1.25 mg Daily n=2 Participants All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Dose Limiting Toxicities (DLT)	0 participants	0 participants	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Best overall response was assessed after every 8 weeks of treatment and at the end of treatment or time of disease progression, up to 1 year.

Population: All enrolled subjects were analyzed for this outcome.

Best overall response is defined as the best response across all time points. Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of disease progression. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is \>=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of \>=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.

Outcome measures

Outcome measures
Measure	Metronomic Oral Topotecan n=3 Participants All subjects received metronomic oral topotecan daily at the assigned dose level.	Oral Topotecan 0.50 mg Daily n=4 Participants All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	Oral Topotecan 0.75 mg Daily n=3 Participants All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	Oral Topotecan 1.0 mg Daily n=14 Participants All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	Oral Topotecan 1.25 mg Daily n=2 Participants All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Best Overall Response Complete Response	0 participants	0 participants	0 participants	0 participants	0 participants
Best Overall Response Partial Response	0 participants	0 participants	0 participants	1 participants	0 participants
Best Overall Response Stable Disease	2 participants	1 participants	2 participants	4 participants	0 participants
Best Overall Response Progressive Disease	0 participants	1 participants	1 participants	2 participants	0 participants
Best Overall Response Not Evaluable	1 participants	2 participants	0 participants	7 participants	2 participants

Adverse Events

Oral Topotecan 0.25 mg Daily

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Oral Topotecan 0.50 mg Daily

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Oral Topotecan 0.75 mg Daily

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Oral Topotecan 1.0 mg Daily

Serious events: 7 serious events

Other events: 13 other events

Deaths: 0 deaths

Oral Topotecan 1.25 mg Daily

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Oral Topotecan 0.25 mg Daily n=3 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1).	Oral Topotecan 0.50 mg Daily n=4 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	Oral Topotecan 0.75 mg Daily n=3 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	Oral Topotecan 1.0 mg Daily n=14 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	Oral Topotecan 1.25 mg Daily n=2 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Ascites	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Nausea	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 1/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Asthenia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Infection	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 1/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 1/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Confusional state	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Delirium	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Vaginal hemorrhage	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.

Other adverse events

Other adverse events
Measure	Oral Topotecan 0.25 mg Daily n=3 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1).	Oral Topotecan 0.50 mg Daily n=4 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	Oral Topotecan 0.75 mg Daily n=3 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	Oral Topotecan 1.0 mg Daily n=14 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	Oral Topotecan 1.25 mg Daily n=2 participants at risk All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 2/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	57.1% 8/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	21.4% 3/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	14.3% 2/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Cardiac disorders Tachycardia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Ear and labyrinth disorders Ear pain	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Eye hemorrhage	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Vision blurred	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	14.3% 2/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	42.9% 6/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal pain upper	66.7% 2/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	14.3% 2/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal tenderness	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Ascites	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Constipation	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 2/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	42.9% 6/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	21.4% 3/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 1/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Dry mouth	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Dysphagia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Nausea	66.7% 2/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	42.9% 6/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 1/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Small intestinal obstruction	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 7/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 1/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Asthenia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Chest pain	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Fatigue	66.7% 2/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	75.0% 3/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 7/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Influenza like illness	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Peripheral edema	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Pain	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 2/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Pyrexia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	21.4% 3/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Hepatobiliary disorders Jaundice	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Cellulitis	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Infection	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	14.3% 2/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Oral candidiasis	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Urinary tract infection	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood creatinine increased	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Neutrophil count decreased	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Neutrophil count increased	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Platelet count increased	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Waist circumference increased	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Weight decreased	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	21.4% 3/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Weight increased	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	28.6% 4/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Fluid overload	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	50.0% 2/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	14.3% 2/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Cognitive disorder	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Dizziness	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	14.3% 2/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Dysgeusia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Headache	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Lethargy	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Peripheral neuropathy	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	14.3% 2/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Paresthesia	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Restless leg syndrome	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Sinus headache	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Depression	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Insomnia	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Nightmare	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Renal and urinary disorders Hydronephrosis	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Perineal pain	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Vaginal hemorrhage	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Exertional dyspnea	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	14.3% 2/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	33.3% 1/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Hypertension	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	7.1% 1/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Hypotension	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/4 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/3 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	21.4% 3/14 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected on day 1 of treatment until one month after the end of study treatment. Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.

Additional Information

Vice President of Scientific Affairs

Accelerated Community Oncology Research Network, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60