Trial Outcomes & Findings for Combination Chemotherapy in Treating Patients With Advanced Stomach, Gastroesophageal, or Esophageal Cancer (NCT NCT01928290)

NCT ID: NCT01928290

Last Updated: 2020-08-25

Results Overview

* Objective response (defined as complete response (CR) + partial response (PR) by RECIST 1.1 criteria) * CR: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

Through completion of treatment (estimated to be 4 months)

Results posted on

2020-08-25

Participant Flow

The study opened to participant enrollment on 11/08/2013 and closed to participant enrollment on 07/23/2018.

Participant milestones

Participant milestones
Measure	Arm A: FOLFIRINOX (HER2-negative) Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Overall Study STARTED	41	26
Overall Study COMPLETED	41	26
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Chemotherapy in Treating Patients With Advanced Stomach, Gastroesophageal, or Esophageal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 Participants Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 Participants Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Total n=67 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	59.5 years n=7 Participants	59 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	26 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=5 Participants	26 Participants n=7 Participants	67 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 (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	25 Participants n=7 Participants	63 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants	26 participants n=7 Participants	67 participants n=5 Participants

PRIMARY outcome

Timeframe: Through completion of treatment (estimated to be 4 months)

Outcome measures

Outcome measures
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 Participants Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 Participants Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Number of Participants With an Objective Response	25 Participants	22 Participants

SECONDARY outcome

Timeframe: Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months)

Duration of time from start of treatment to time of progression or death, whichever occurs first.

Outcome measures

Outcome measures
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 Participants Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 Participants Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Progression Free Survival	8.4 months Interval 6.8 to 12.2	13.8 months Interval 10.0 to 19.8

SECONDARY outcome

Timeframe: Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months)

Duration of time from start of treatment to time of progression. Progression is defined as At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 Participants Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 Participants Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Time to Progression (TTP)	8.0 months Interval 6.7 to 12.0	13.9 months Interval 9.9 to 19.5

SECONDARY outcome

Timeframe: Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months)

Overall survival is defined as the time interval from date of diagnosis to date of death from any cause.

Outcome measures

Outcome measures
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 Participants Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 Participants Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Overall Survival (OS)	15.5 months Interval 10.6 to 19.6	19.6 months Interval 16.1 to 24.6

SECONDARY outcome

Timeframe: Through completion of treatment (estimated to be 4 months)

* Clinical benefit rate is the percentage of combined patients who have achieved complete response (CR), partial response (PR), and stable disease (SD) * CR: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm * PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters * SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 Participants Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 Participants Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Clinical Benefit Rate	33 Participants	22 Participants

SECONDARY outcome

Timeframe: Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months)

Time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented

Outcome measures

Outcome measures
Measure	Arm A: FOLFIRINOX (HER2-negative) n=25 Participants Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=22 Participants Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Duration of Response	5.8 months Interval 3.5 to 13.5	10.5 months Interval 7.9 to 18.4

SECONDARY outcome

Timeframe: 30 days after completion of treatment (estimated to be 5 months)

Outcome measures

Outcome measures
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 Participants Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 Participants Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Neutropenic entercolitis	0 participants	1 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Anemia	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Febrile neutropenia	2 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Anal Fistula	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Diarrhea	4 participants	5 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Hematemesis	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Nausea	2 participants	2 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Peripheral ischemia	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Vomiting	3 participants	1 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Fatigue	4 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Laparoscopy surgery	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Pain	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Sepsis	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Lung infection	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Pneumonia	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Hypernatremia	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Neutrophil count decreased	19 participants	8 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Platelet count decreased	3 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Anorexia	3 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Dehydration	4 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Hypokalemia	1 participants	2 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Back pain	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Peripheral sensory neuropathy	2 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Syncope	1 participants	1 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Dyspnea	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Pleural embolism	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Skin infection	1 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Thromboembolic event	4 participants	0 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Abdominal pain	0 participants	1 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Enterocolitis	0 participants	1 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Hemorrhoids	0 participants	1 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events G-tube infection	0 participants	1 participants
Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events Alkaline phosphatase increased	0 participants	1 participants

Adverse Events

Arm A: FOLFIRINOX (HER2-negative)

Serious events: 18 serious events

Other events: 41 other events

Deaths: 32 deaths

Arm B: FOLFIRINOX & Trastuzumab (HER2-positive)

Serious events: 8 serious events

Other events: 26 other events

Deaths: 20 deaths

Serious adverse events

Other adverse events

Additional Information

Haeseong Park, M.D.

Washington University School of Medicine

Phone: 314-747-6268

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 participants at risk Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 participants at risk Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Gastrointestinal disorders Abdominal pain	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Metabolism and nutrition disorders Anorexia	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Cardiac disorders Atrial fibrillation	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death due to disease progression	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Metabolism and nutrition disorders Dehydration	7.3% 3/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Diarrhea	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	11.5% 3/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
General disorders Edema limbs	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Infections and infestations Enterocolitis	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
General disorders Fatigue	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Blood and lymphatic system disorders Febrile neutropenia	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
General disorders Fever	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Infections and infestations G-Tube infection	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Hemorrhoids	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Surgical and medical procedures Laparoscopy	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Nausea	7.3% 3/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Neutropenic Enterocolitis	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
General disorders Pain	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Peripheral ischemia	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Respiratory, thoracic and mediastinal disorders Pneumonia	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Vascular disorders Pulmonary embolism	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Infections and infestations Sepsis	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Infections and infestations Skin infection	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Injury, poisoning and procedural complications Spinal fracture	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Vascular disorders Thromboembolic event	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Vomiting	7.3% 3/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.

Other adverse events
Measure	Arm A: FOLFIRINOX (HER2-negative) n=41 participants at risk Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Arm B: FOLFIRINOX & Trastuzumab (HER2-positive) n=26 participants at risk Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 \& 15. Oxaliplatin 85 mg/m2 IV on Days 1 \& 15. Leucovorin 400 mg/m2 IV on Days 1 \& 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.
Gastrointestinal disorders Abdominal cramping	9.8% 4/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Abdominal pain	26.8% 11/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	19.2% 5/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Skin and subcutaneous tissue disorders Acne	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Nervous system disorders Agitation	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Investigations Alanine aminotransferase increased	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Investigations Alkaline phosphatase increased	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Immune system disorders Allergic reaction	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Skin and subcutaneous tissue disorders Alopecia	48.8% 20/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	23.1% 6/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Nervous system disorders Amnesia	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Anal Fistula	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Blood and lymphatic system disorders Anemia	7.3% 3/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Metabolism and nutrition disorders Anorexia	46.3% 19/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	23.1% 6/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Psychiatric disorders Anxiety	12.2% 5/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	7.7% 2/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Musculoskeletal and connective tissue disorders Back pain	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	11.5% 3/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Renal and urinary disorders Bladder pain	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Bloating	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	15.4% 4/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Investigations Blood bilirubin increased	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Blood in stool	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Eye disorders Blurred vision	12.2% 5/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Musculoskeletal and connective tissue disorders Bone pain	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Skin and subcutaneous tissue disorders Brittle nails	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Injury, poisoning and procedural complications Bruising	9.8% 4/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	7.7% 2/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Infections and infestations Catheter related infection	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Blood and lymphatic system disorders Chest tightening	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
General disorders Chills	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	23.1% 6/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Skin and subcutaneous tissue disorders Cold sores on the nose	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Respiratory, thoracic and mediastinal disorders Cold symptoms	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Colitis	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Constipation	39.0% 16/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	15.4% 4/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Respiratory, thoracic and mediastinal disorders Cough	17.1% 7/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	15.4% 4/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Skin and subcutaneous tissue disorders Crack in fingernails	0.00% 0/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	3.8% 1/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Musculoskeletal and connective tissue disorders Cramping	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Metabolism and nutrition disorders Dehydration	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Psychiatric disorders Depression	17.1% 7/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	7.7% 2/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Diarrhea	61.0% 25/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	46.2% 12/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Nervous system disorders Dizziness	31.7% 13/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	11.5% 3/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Eye disorders Double vision	2.4% 1/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.
Gastrointestinal disorders Dry mouth	4.9% 2/41 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.	0.00% 0/26 • Adverse events were collected from start of treatment through 30 days following the last day of study treatment (up to 4 cycles following disease maximal response). All-cause mortality was collected through end of participant follow-up. For purposes of this study, abnormal lab values will only be collected and documented if they are clinically significant. Once a patient begins maintenance therapy, adverse events will no longer be collected and documented.