Trial Outcomes & Findings for A Study of Irinotecan Plus Cetuximab With or Without Enzastaurin in Participants With Colorectal Cancer (NCT NCT00437268)

Last Updated: 2020-07-21

Results Overview

PFS was defined as the time from the date of study enrollment to the first date of progressive disease or death from any cause. For participants not known to have died as of the data cut-off date and who did not have progressive disease, PFS was censored at the date of last visit with adequate assessment. For participants who received subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy. The PFS probability values were multiplied by 100 to obtain the percentage values.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

At 6 months from randomization

Results posted on

2020-07-21

Participant Flow

Participant flow reports those participants who discontinued from study drug.

Participant milestones

Participant milestones
Measure	Enzastaurin+Irinotecan+Cetuximab Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 milligrams per square meter (mg/m\^2), intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 of Cycle 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Overall Study STARTED	13	13
Overall Study Received at Least 1 Dose of Study Drug	13	13
Overall Study Protocol Qualified (PQ) Participant	13	12
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	13	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Enzastaurin+Irinotecan+Cetuximab Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 milligrams per square meter (mg/m\^2), intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 of Cycle 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	2	2
Overall Study Progressive disease	9	9
Overall Study Physician Decision	1	0
Overall Study Death	0	1

Baseline Characteristics

A Study of Irinotecan Plus Cetuximab With or Without Enzastaurin in Participants With Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enzastaurin+Irinotecan+Cetuximab n=13 Participants Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab n=13 Participants Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Total n=26 Participants Total of all reporting groups
Age, Continuous	52.5 years STANDARD_DEVIATION 12.45 • n=5 Participants	59.5 years STANDARD_DEVIATION 10.28 • n=7 Participants	56.0 years STANDARD_DEVIATION 11.75 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Fully Active	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Ambulatory, Restricted Strenuous Activity	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Adjuvant Therapy Status Yes	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Adjuvant Therapy Status No	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Basis for Initial Diagnosis Histopathologic	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Basis for Initial Diagnosis Cytologic	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Stage of Disease at Initial Diagnosis Stage IIB	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Stage of Disease at Initial Diagnosis Stage IIIB	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Stage of Disease at Initial Diagnosis Stage IIIC	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Stage of Disease at Initial Diagnosis Stage IV	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Disease Type at Initial Diagnosis Adenocarcinoma	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Disease Type at Initial Diagnosis Mucinous Adenocarcinoma	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Disease Type at Initial Diagnosis Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 6 months from randomization

Population: Protocol qualified population: All randomized participants who received at least 1 dose of study drug and did not develop a severe infusion reaction to cetuximab after the first dose. Participants censored: Irinotecan +Cetuximab+Enzastaurin = 1; Irinotecan +Cetuximab =2.

Outcome measures

Outcome measures
Measure	Enzastaurin+Irinotecan+Cetuximab n=13 Participants Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab n=12 Participants Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Percentage of Participants With Progression-Free Survival (PFS) at 6 Months (PFS Rate)	26 percentage of participants Interval 1.0 to 51.0	23 percentage of participants Interval 0.0 to 49.0

SECONDARY outcome

Timeframe: Baseline to measured progressive disease up to 13.2 months

Population: Protocol qualified population: All randomized participants who received at least 1 dose of study drug and did not develop a severe infusion reaction to cetuximab after the first dose.

Tumor response rate was defined as number of participants with overall best response of complete response (CR) or partial response (PR) over number of protocol qualified participants using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) Guidelines. CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions, with no new lesions appearing. Percentage of participants = (Number of participants with overall best response of CR or PR/Number of protocol qualified participants) x 100.

Outcome measures

Outcome measures
Measure	Enzastaurin+Irinotecan+Cetuximab n=13 Participants Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab n=12 Participants Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Tumor Response Rate)	7.7 percentage of participants Interval 0.2 to 36.0	16.7 percentage of participants Interval 2.1 to 48.4

SECONDARY outcome

Timeframe: Time of response to progressive disease up to 13.2 months

Population: Participants with a CR or PR. No participants were censored.

The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of disease progression or death from any cause. According to the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, CR was defined as the disappearance of all tumor lesions and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions, with no new lesions appearing. For participants who died, the duration of response was censored at death. For participants still alive, duration of response was censored at the last visit with adequate assessment.

Outcome measures

Outcome measures
Measure	Enzastaurin+Irinotecan+Cetuximab n=1 Participants Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab n=2 Participants Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Duration of Response	6.9 months The confidence interval was not estimable due to too few data points	12.6 months Interval 12.0 to 13.2

SECONDARY outcome

Timeframe: Randomization to date of death from any cause up to 21.9 months

Population: Protocol qualified population: All randomized participants who received at least 1 dose of study drug and did not develop a severe infusion reaction to cetuximab after the first dose. Censored participants: Enzastaurin+Irinotecan+Cetuximab = 4; Irinotecan+Cetuximab = 4.

OS was defined as the time in months from the date of study enrollment to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last contact date.

Outcome measures

Outcome measures
Measure	Enzastaurin+Irinotecan+Cetuximab n=13 Participants Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab n=12 Participants Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Overall Survival (OS)	8.5 months Interval 5.5 to 16.4	8.0 months Interval 4.5 to 21.9

SECONDARY outcome

Timeframe: Baseline to disease progression (up to 13.2 months)

Population: Protocol qualified population: All randomized participants who received at least 1 dose of study drug and did not develop a severe infusion reaction to cetuximab after the first dose.

The overall disease control rate for each treatment arm was calculated as percent of participants with overall response of complete response (CR), partial response (PR) or stable disease (SD) over number of protocol qualified population. According to the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, CR was defined as the disappearance of all tumor lesions, PR was defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions, progressive disease (PD) was defined as at least 20% increase in sum of LD of target lesions, and SD was defined as small changes that did not meet above criteria. Percentage of participants = (Number of participants with overall best response of CR, PR, or SD/Number of protocol qualified participants) x 100.

Outcome measures

Outcome measures
Measure	Enzastaurin+Irinotecan+Cetuximab n=13 Participants Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab n=12 Participants Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Percentage of Participants With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate)	38.5 percentage of participants Interval 13.9 to 68.4	50.0 percentage of participants Interval 21.1 to 78.9

SECONDARY outcome

Timeframe: Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up)

Population: The safety population included all randomized and treated participants.

Clinically significant events were defined as serious and other non-serious AEs. Participants who died due to progressive disease (PD) or and adverse events (AEs) while on treatment and or died during the 30 day post-treatment are included. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	Enzastaurin+Irinotecan+Cetuximab n=13 Participants Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab n=13 Participants Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Number of Participants With Adverse Events (AEs) or Who Died Non-serious AEs	13 Participants	13 Participants
Number of Participants With Adverse Events (AEs) or Who Died Serious AEs	8 Participants	6 Participants
Number of Participants With Adverse Events (AEs) or Who Died Deaths Due to PD	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) or Who Died Deaths Due to AEs	0 Participants	1 Participants
Number of Participants With Adverse Events (AEs) or Who Died Deaths in 30-day follow-up	0 Participants	1 Participants

Adverse Events

Enzastaurin+Irinotecan+Cetuximab

Serious events: 8 serious events

Other events: 13 other events

Deaths: 0 deaths

Irinotecan+Cetuximab

Serious events: 6 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Enzastaurin+Irinotecan+Cetuximab n=13 participants at risk Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 milligrams per square meter (mg/m\^2), intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 of Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease	Irinotecan+Cetuximab n=13 participants at risk Irinotecan: 300 mg/m\^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m\^2 intravenously on Day 1, then 250 mg/m\^2 on Days 8 and 15 in Cycle 1, then 250 mg/m\^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
Blood and lymphatic system disorders Anaemia	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Blood and lymphatic system disorders Febrile neutropenia	15.4% 2/13 • Number of events 2 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Blood and lymphatic system disorders Neutropenia	15.4% 2/13 • Number of events 3 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	15.4% 2/13 • Number of events 2 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Ascites	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Diarrhoea	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Nausea	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Rectal haemorrhage	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Small intestinal obstruction	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
General disorders Fatigue	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
General disorders Multi-organ failure	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Hepatobiliary disorders Gallbladder obstruction	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Infections and infestations Anorectal cellulitis	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Infections and infestations Bacteraemia	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Infections and infestations Clostridium difficile colitis	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Metabolism and nutrition disorders Dehydration	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Metabolism and nutrition disorders Hyperkalaemia	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Psychiatric disorders Mental status changes	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Reproductive system and breast disorders Vaginal haemorrhage	11.1% 1/9 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	11.1% 1/9 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.7% 1/13 • Number of events 1 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
Vascular disorders Hypotension	7.7% 1/13 • Number of events 2 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.	0.00% 0/13 • Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.