Trial Outcomes & Findings for A Phase I Trial Evaluating mFOLFOX6 and Avastin With Nexavar as First-Line Treatment for Metastatic Colorectal Cancer (NCT NCT00779311)

Last Updated: 2011-11-02

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

8 participants

Primary outcome timeframe

MTD was assessed during the first 2 cycles of treatment (i.e., the first 4 weeks of treatment since cycle length is 2 weeks)

Results posted on

2011-11-02

Participant Flow

Three community oncology research sites across the US within the ACORN Network participated in this study. Enrollment started in October 2008 and was closed early in April 2010 due to two subjects experiencing DLT at the lowest dose level.

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. All subjects received mFOLFOX6, bevacizumab, and sorafenib. Subjects were assigned to a Dosage Level at the time of enrollment.

Participant milestones

Participant milestones
Measure	Dose Level (DL) 1 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.	Dose Level (DL) 2 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.	Dose Level (DL) 3 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.	Dose Level (DL) 4 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.	Dose Level (DL) 5 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.
Overall Study STARTED	8	0	0	0	0
Overall Study Dose Limiting Toxicity (DLT) Evaluation	6	0	0	0	0
Overall Study COMPLETED	8	0	0	0	0
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase I Trial Evaluating mFOLFOX6 and Avastin With Nexavar as First-Line Treatment for Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level (DL) 1 for MTD Determination n=8 Participants All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.	Dose Level (DL) 2 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.	Dose Level (DL) 3 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.	Dose Level (DL) 4 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.	Dose Level (DL) 5 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.	Total n=8 Participants Total of all reporting groups
Age Categorical <=18 years	0 participants n=5 Participants	—	—	—	—	0 participants n=10 Participants
Age Categorical Between 18 and 65 years	3 participants n=5 Participants	—	—	—	—	3 participants n=10 Participants
Age Categorical >=65 years	5 participants n=5 Participants	—	—	—	—	5 participants n=10 Participants
Age Continuous	62.0 years STANDARD_DEVIATION 11.40 • n=5 Participants	—	—	—	—	62.0 years STANDARD_DEVIATION 11.40 • n=10 Participants
Gender Female	3 participants n=5 Participants	—	—	—	—	3 participants n=10 Participants
Gender Male	5 participants n=5 Participants	—	—	—	—	5 participants n=10 Participants
Region of Enrollment United States	8 participants n=5 Participants	—	—	—	—	8 participants n=10 Participants

PRIMARY outcome

Timeframe: MTD was assessed during the first 2 cycles of treatment (i.e., the first 4 weeks of treatment since cycle length is 2 weeks)

Population: 3 patients (pts) were enrolled at DL 1 with 1/3 experiencing DLT, so 3 additional pts were enrolled at DL 1. 2 of those additional pts were not evaluable for DLT assessment and were replaced. 2 more pts were enrolled for a total of 8 pts, and 1 of these pts experienced a DLT. All of the 8 pts enrolled received sorafenib at DL 1.

Outcome measures

Outcome measures
Measure	Dose Level (DL) 1 for MTD Determination n=8 Participants All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.	Dose Level (DL) 2 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.	Dose Level (DL) 3 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.	Dose Level (DL) 4 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.	Dose Level (DL) 5 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.
Determination of the Maximum Tolerated Dose (MTD) of Sorafenib When Given in Combination With mFOLFOX6 and Bevacizumab	200 mg every other day	—	—	—	—

SECONDARY outcome

Timeframe: PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever came first.

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.

Outcome measures

Outcome measures
Measure	Dose Level (DL) 1 for MTD Determination n=8 Participants All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.	Dose Level (DL) 2 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.	Dose Level (DL) 3 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.	Dose Level (DL) 4 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.	Dose Level (DL) 5 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.
Determination of Progression Free Survival (PFS) Among Patients on This Regimen	10.61 Months Interval 3.61 to 13.4	—	—	—	—

SECONDARY outcome

Timeframe: The PCM questionnaire was administered on day 1 of each cycle (approximately every 2 weeks) during study treatment.

Population: The number of patients out of the total sample of 8 patients who reported severe (rated as \>=7) symptoms as assessed by the PCM. Symptoms with 0 patients reporting severe symptoms have been omitted.

The subject answers questions from the following 6 categories: general physical symptoms, treatment side effects, distress, despair, impaired performance, and impaired ambulation. Each question has a scale from 0 through 10, where 0 is not a problem and 10 is as bad as possible. The frequency of patient reported severe (rated as \>=7) symptoms reported from the set of symptoms assessed by the PCM.

Outcome measures

Outcome measures
Measure	Dose Level (DL) 1 for MTD Determination n=8 Participants All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.	Dose Level (DL) 2 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.	Dose Level (DL) 3 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.	Dose Level (DL) 4 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.	Dose Level (DL) 5 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Fatigue	3 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Change in taste	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Mouth sores/ulcers	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Sore throat	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Trouble swallowing	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Day sweat	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Night sweat	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Reduced sexual enjoyment, interest, or performance	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Heartburn	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Nausea	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Problem with urination	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Bruising	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen New lump/mass	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Hair loss	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Nails change	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Joint pain	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Muscle aches	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Weakness of body parts	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Burning sensation in hands or feet	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Numbness/tingling	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Trouble sleeping at night	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Pain	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Attend paid job	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Attend social activity	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Hard work or activity	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Household work	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Light work or activity	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Run	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Walk	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Crying/feeling like crying	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Feeling helpless	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Feeling hopeless	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Lost interest in people	1 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Nervous, tense, anxious	2 Participants	—	—	—	—
Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen Worry	2 Participants	—	—	—	—

Adverse Events

Dose Level (DL) 1 for MTD Determination

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

Dose Level (DL) 2 for MTD Determination

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dose Level (DL) 3 for MTD Determination

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dose Level (DL) 4 for MTD Determination

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dose Level (DL) 5 for MTD Determination

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level (DL) 1 for MTD Determination n=8 participants at risk All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.	Dose Level (DL) 2 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.	Dose Level (DL) 3 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.	Dose Level (DL) 4 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.	Dose Level (DL) 5 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.
Gastrointestinal disorders Diarrhea	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Chest pain	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Gastroenteritis	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Pneumonia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Dysgeusia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Lethargy	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Renal and urinary disorders Renal failure acute	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Dyspnea	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.

Other adverse events

Other adverse events
Measure	Dose Level (DL) 1 for MTD Determination n=8 participants at risk All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.	Dose Level (DL) 2 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.	Dose Level (DL) 3 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.	Dose Level (DL) 4 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.	Dose Level (DL) 5 for MTD Determination All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.
Blood and lymphatic system disorders Anemia	37.5% 3/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Neutropenia	62.5% 5/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Thrombocytopenia	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Lacrimation increased	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal hernia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Constipation	62.5% 5/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Diarrhea	50.0% 4/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Dry mouth	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Dyspepsia	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Dysphagia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Mouth ulceration	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Nausea	62.5% 5/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Proctalgia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Rectal hemorrhage	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Stomatitis	37.5% 3/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Vomiting	37.5% 3/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Chest discomfort	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Chest pain	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Chills	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Fatigue	62.5% 5/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Mucosal inflammation	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Pyrexia	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Temperature intolerance	37.5% 3/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Thrombosis in device	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Fungal infection	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Laryngitis bacterial	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Sinusitis	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Tooth abscess	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Upper respiratory tract infection	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Urinary tract infection	37.5% 3/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood albumin decreased	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood creatinine increased	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood urea increased	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Weight decreased	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Decreased appetite	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hyperglycemia	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hyperkalemia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypoalbuminemia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypokalemia	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypomagnesemia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hyponatremia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypophosphatemia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Pain in extremity	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Dizziness	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Dysesthesia	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Dysgeusia	50.0% 4/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Headache	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Neuropathy peripheral	37.5% 3/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Anxiety	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Insomnia	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Cough	37.5% 3/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Dyspnea	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Epistaxis	50.0% 4/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Hiccups	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Alopecia	37.5% 3/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Cold sweat	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Increased tendency to bruise	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Nail disorder	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Pruritis	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Rash	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Hypertension	25.0% 2/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Orthostatic hypotension	12.5% 1/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Peripheral coldness	50.0% 4/8 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.	— 0/0 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment. Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle (every other week) by either the research coordinator, treating physician, or other appropriate sub-investigator.

Additional Information

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Accelerated Community Oncology Research Network, Inc.

Phone: 901-435-5570

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Prior to publication or presentation of Sponsored Research results, Researcher agrees to provide Bayer with such presentation, abstract, or manuscript at least 30 days prior to its presentation or submission for the sole purpose of allowing Bayer to redact Confidential Information and protect any existing or future patents.
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Restriction type: OTHER