Trial Outcomes & Findings for Capecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer (NCT NCT00022698)

Last Updated: 2016-04-15

Results Overview

Objective Response Rate (ORR) is defined as the percentage of participants with complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST 1.0). CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as a greater than or equal to (\>/=) 30% decrease in the sum of the longest diameter (LD) of the target lesions, taking as reference the baseline sum of LD. Participants who did not have a post-baseline tumor measurement were considered non-responders in the assessment of ORR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

Approximately 43 Months

Results posted on

2016-04-15

Participant Flow

A total of 67 participants were enrolled in the study, which was conducted from 18 May 2001 to 9 December 2004 at 18 study centers in the United States.

Data for participants who completed 12 cycles of the study treatment is presented.

Participant milestones

Participant milestones
Measure	Cohort 1, Initial Regimen: (Capecitabine + Irinotecan) Participants received capecitabine (Xeloda) 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute intravenous (IV) infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).
Overall Study STARTED	15	52
Overall Study COMPLETED	7	17
Overall Study NOT COMPLETED	8	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1, Initial Regimen: (Capecitabine + Irinotecan) Participants received capecitabine (Xeloda) 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute intravenous (IV) infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).
Overall Study Adverse Event	5	9
Overall Study Death	0	2
Overall Study Failure to return	0	1
Overall Study Refused treatment	0	2
Overall Study Insufficient therapeutic response	2	14
Overall Study Administrative /other	1	7

Baseline Characteristics

Capecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1, Initial Regimen: (Capecitabine + Irinotecan) n=15 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total n=67 Participants Total of all reporting groups
Age, Continuous	63.1 years STANDARD_DEVIATION 8.3 • n=5 Participants	61.4 years STANDARD_DEVIATION 11.1 • n=7 Participants	61.8 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	21 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	31 Participants n=7 Participants	37 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 43 Months

Population: The All Patients Population included participants who received at least one dose of study drug in Cohort 1 or Cohort 2.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=15 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) Total of all reporting groups.
Tumor Response Rate Based on Tumor Measurement as Per Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST 1.0) CR	7 percentage of participants	2 percentage of participants	—
Tumor Response Rate Based on Tumor Measurement as Per Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST 1.0) PR	40 percentage of participants	42 percentage of participants	—

SECONDARY outcome

Timeframe: Approximately 43 Months

Population: The All Patients Population included participants who received at least one dose of study drug in Cohort 1 or Cohort 2.

Time to disease progression was assessed as the time from start of treatment to the time the participant was first recorded as having disease progression or died due to causes other than disease progression. If a participant never progressed while being followed, he/she was censored at the date of the last tumor assessment or the date of the last dose if no post-baseline tumor measurement was available.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=15 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) Total of all reporting groups.
Time to Disease Progression	6.1 months Interval 3.4 to 9.0	7.6 months Interval 5.8 to 8.7	—

SECONDARY outcome

Timeframe: Approximately 43 Months

Population: The All Patients Population included participants who received at least one dose of study drug in Cohort 1 or Cohort 2.

Time to treatment failure was assessed as the time from start of treatment to the time the participant was withdrawn due to any of the reasons such as adverse events, progressive disease, insufficient therapeutic response, death, failure to return, or refused treatment, did not cooperate or withdrew consent.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=15 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) Total of all reporting groups.
Time to Treatment Failure	5.8 months Interval 2.4 to 9.2	7.3 months Interval 4.6 to 9.5	—

SECONDARY outcome

Timeframe: Up to Month 12

Population: The All Patients Population included participants who received at least one dose of study drug in Cohort 1 or Cohort 2.

Survival was measured as the time from start of treatment to the date of death or till one year whichever occurred first.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=15 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) Total of all reporting groups.
Percentage of Participants With One-year Survival	67 percentage of participants Interval 43.0 to 91.0	71 percentage of participants Interval 58.0 to 83.0	—

SECONDARY outcome

Timeframe: Approximately 43 Months

Population: The All Patients Population included participants who received at least one dose of study drug in Cohort 1 or Cohort 2.

Overall Survival is defined as the time from start of treatment to the date of death. Participants who did not die were censored at the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=15 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) Total of all reporting groups.
Overall Survival	22.9 months Interval 10.1 to 28.2	20.5 months Interval 14.9 to 30.0	—

SECONDARY outcome

Timeframe: Approximately 43 Months

Population: The All Patients Population included participants who received at least one dose of study drug in Cohort 1 or Cohort 2.

The time to objective response is defined as the time from start of treatment to the date of first objective response. Participants who never responded during study were censored at the last tumor assessment or the date of last dose, whichever was later, or at the date of death if occurring prior to response.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=15 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) Total of all reporting groups.
Time To Objective Response	5.5 months Interval 2.7 to 8.6	4.3 months Interval 2.6 to 9.6	—

SECONDARY outcome

Timeframe: Approximately 43 Months

Population: The All Patients Population included participants who received at least one dose of study drug in Cohort 1 or Cohort 2. Data for participants present at the time of assessment was used for analysis.

Duration of overall response was assessed from the time that measurement criteria were first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease was documented. It was analyzed for responders only. Participants without observed progressive disease after an objective response were censored at the date of the last tumor assessment.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=7 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=23 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) Total of all reporting groups.
Duration of Overall Response	7.0 months Interval 2.6 to 9.2	7.7 months Interval 5.8 to 11.5	—

SECONDARY outcome

Timeframe: Approximately 43 Months

The duration of overall complete response was assessed from the time that measurement criteria were met for complete response until the first date that recurrent or progressive disease was objectively documented. Participants without observed progressive disease after an objective complete response were censored at the date of the last tumor assessment.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=1 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=1 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) Total of all reporting groups.
Duration of Overall Complete Response	12.45 months	12.68 months	—

SECONDARY outcome

Timeframe: Approximately 43 Months

Population: The Safety Population consisted of all participants who received at least 1 dose of any study drug and had at least one post-baseline safety assessment. This included participants in Cohort 1 and Cohort 2.

An adverse event (AEs) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. A serious adverse event is defined as any event which was fatal (resulted in death), life-threatening (with immediate risk of death), resulted in a new or prolongation of a current hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, considered medically significant by the investigator, required intervention to prevent one or more of the outcomes listed above.

Outcome measures

Outcome measures
Measure	Cohort 1, Initial Regimen:(Capecitabine + Irinotecan) n=15 Participants Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 Participants Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Total Participants (Cohort 1 + Cohort 2) n=67 Participants Total of all reporting groups.
Number of Participants With Any Adverse Events, Serious Adverse Events and Deaths Any AEs	15 Number of participants	52 Number of participants	67 Number of participants
Number of Participants With Any Adverse Events, Serious Adverse Events and Deaths SAEs	10 Number of participants	25 Number of participants	35 Number of participants
Number of Participants With Any Adverse Events, Serious Adverse Events and Deaths Deaths During Study	0 Number of participants	3 Number of participants	3 Number of participants
Number of Participants With Any Adverse Events, Serious Adverse Events and Deaths Deaths During Follow-up	13 Number of participants	23 Number of participants	36 Number of participants

Adverse Events

Cohort 1, Initial Regimen: (Capecitabine + Irinotecan)

Serious events: 10 serious events

Other events: 15 other events

Deaths: 0 deaths

Cohort 2, Amended Regimen: (Capecitabine + Irinotecan)

Serious events: 25 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cohort 1, Initial Regimen: (Capecitabine + Irinotecan) n=15 participants at risk Participants received capecitabine 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute IV infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).	Cohort 2, Amended Regimen: (Capecitabine + Irinotecan) n=52 participants at risk Participants received capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute IV infusion on Day 1 and 8, every 3 weeks. A total of 12 cycles of treatment was administered. At the discretion of the investigator, participants who were responding or whose disease was stable were permitted to continue capecitabine/irinotecan combination therapy until progressive disease was documented in the post-study treatment phase. Participants not receiving post-study treatment were followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).
Gastrointestinal disorders Diarrhoea	13.3% 2/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	9.6% 5/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	11.5% 6/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Gastrointestinal disorders Constipation	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Gastrointestinal disorders Enterocolitis	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Gastrointestinal disorders Ileitis	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Gastrointestinal disorders Ileus	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Gastrointestinal disorders Colitis	6.7% 1/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	0.00% 0/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Metabolism and nutrition disorders Dehydration	20.0% 3/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	7.7% 4/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Metabolism and nutrition disorders Hyperglycaemia	6.7% 1/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	0.00% 0/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Vascular disorders Deep vein thrombosis	13.3% 2/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	5.8% 3/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Vascular disorders Aortic thrombosis	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Vascular disorders Haemorrhage	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Vascular disorders Vasoconstriction	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Infections and infestations Cellulitis	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Infections and infestations Localised infection	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Infections and infestations Pneumonia staphylococcal	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Infections and infestations Pneumonia	6.7% 1/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	0.00% 0/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Infections and infestations Sepsis	6.7% 1/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	0.00% 0/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	13.3% 2/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	3.8% 2/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Blood and lymphatic system disorders Febrile neutropenia	6.7% 1/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Cardiac disorders Atrial fibrillation	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
General disorders Pyrexia	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	1.9% 1/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	6.7% 1/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	0.00% 0/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.
Renal and urinary disorders Renal failure acute	6.7% 1/15 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.	0.00% 0/52 • Approximately 43 Months Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post-baseline.