Trial Outcomes & Findings for S1406 Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer (NCT NCT02164916)

NCT ID: NCT02164916

Last Updated: 2020-12-30

Results Overview

From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 106 participants
• Primary outcome timeframe: Up to 3 years from randomization
• Results posted on: 2020-12-30

Participant Flow

Participant milestones

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO
Overall Study STARTED	52	54
Overall Study Eligible	50	49
Overall Study Cross-over to Arm II	24	0
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	52	54

Reasons for withdrawal

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO
Overall Study Adverse Event	3	8
Overall Study Death	1	1
Overall Study Refusal unrelated to adverse event	3	7
Overall Study Progression	37	26
Overall Study Not protocol specified	5	1
Overall Study Reason under review	1	6
Overall Study Not eligible	2	5

Baseline Characteristics

S1406 Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer

Baseline characteristics by cohort

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) n=50 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) n=49 Participants Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Total n=99 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	60 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	21 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	28 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	46 Participants n=7 Participants	94 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	1 Participants n=5 Participants	4 Participants n=7 Participants	5 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	49 Participants n=5 Participants	43 Participants n=7 Participants	92 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	1 Participants n=7 Participants	1 Participants n=5 Participants
Prior treatment with Irinotecan Yes	19 participants n=5 Participants	20 participants n=7 Participants	39 participants n=5 Participants
Prior treatment with Irinotecan No	31 participants n=5 Participants	29 participants n=7 Participants	60 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 years from randomization

Population: Eligible and analyzable patients.

From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.

Outcome measures

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) n=50 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) n=49 Participants Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Crossover: Vemurafenib + Cetuximab + Irinotecan Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	2.0 months Interval 1.8 to 2.1	4.3 months Interval 3.6 to 5.7	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: Eligible patients who received any treatment and were assessed for adverse events are included in this summary.

Only adverse events that are possibly, probably or definitely related to study drug are reported.

Outcome measures

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) n=46 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) n=46 Participants Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Crossover: Vemurafenib + Cetuximab + Irinotecan n=21 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Generalized muscle weakness	1 Participants	1 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Hyperkalemia	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Abdominal pain	1 Participants	2 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Alkaline phosphatase increased	2 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Allergic reaction	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Anaphylaxis	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Anemia	0 Participants	6 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Anorexia	2 Participants	3 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Arthralgia	0 Participants	3 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Arthritis	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Blood bilirubin increased	1 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Cardiac disorders - Other, specify	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Colitis	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Colonic obstruction	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Creatinine increased	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Dehydration	3 Participants	5 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Diarrhea	6 Participants	11 Participants	7 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Electrocardiogram QT corrected interval prolonged	0 Participants	1 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Fatigue	7 Participants	7 Participants	7 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Febrile neutropenia	2 Participants	5 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Gastric hemorrhage	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Hypocalcemia	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Hypokalemia	1 Participants	5 Participants	2 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Hypomagnesemia	2 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Hyponatremia	1 Participants	2 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Infusion related reaction	1 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Insomnia	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Lower gastrointestinal hemorrhage	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Lung infection	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Lymphocyte count decreased	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Metabolic acidosis	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Mucositis oral	0 Participants	2 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Myalgia	0 Participants	2 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Nausea	1 Participants	9 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Neutrophil count decreased	3 Participants	15 Participants	2 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Pain	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Palmar-plantar erythrodysesthesia syndrome	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Pancreatitis	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Papulopustular rash	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Photosensitivity	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Platelet count decreased	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Pruritus	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Rash acneiform	3 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Rash maculo-papular	0 Participants	1 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Rash pustular	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Sepsis	0 Participants	2 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Thromboembolic event	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Treatment related secondary malignancy	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Urinary tract infection	1 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Vomiting	1 Participants	5 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug Weight loss	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug White blood cell decreased	0 Participants	8 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years from randomization

Population: Eligible and analyzable patients

From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Outcome measures

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) n=50 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) n=49 Participants Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Crossover: Vemurafenib + Cetuximab + Irinotecan Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival	5.9 months Interval 3.0 to 9.9	9.6 months Interval 7.5 to 13.1	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years from randomization

Population: All eligible and analyzable patients with measurable disease.

Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Outcome measures

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) n=47 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) n=44 Participants Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Crossover: Vemurafenib + Cetuximab + Irinotecan Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Response Rate Partial Response	1 Participants	3 Participants	—
Overall Response Rate Unconfirmed Partial Response	1 Participants	4 Participants	—
Overall Response Rate Stable/No Response	8 Participants	22 Participants	—
Overall Response Rate Increasing Disease	25 Participants	7 Participants	—
Overall Response Rate Symptomatic Deterioration	6 Participants	1 Participants	—
Overall Response Rate Assessment Inadequate	6 Participants	7 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years from randomization

Population: All eligible and analyzable patients.

From date of Step 3 Crossover registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.

Outcome measures

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) n=22 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Crossover: Vemurafenib + Cetuximab + Irinotecan Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1	5.8 months Interval 2.8 to 6.1	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years from randomization

Population: Eligible and analyzable patients

From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Outcome measures

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) n=22 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Crossover: Vemurafenib + Cetuximab + Irinotecan Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1	12.1 months Interval 4.5 to 12.5	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years from randomization

Population: Eligible and analyzable patients with measurable disease.

Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Outcome measures

Measure	Arm I (Cetuximab, Irinotecan Hydrochloride) n=18 Participants Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib) Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Crossover: Vemurafenib + Cetuximab + Irinotecan Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Response Rate in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1 Increasing Disease	5 Participants	—	—
Overall Response Rate in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1 Partial Response	2 Participants	—	—
Overall Response Rate in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1 Unconfirmed Partial Response	1 Participants	—	—
Overall Response Rate in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1 Stable/No Response	10 Participants	—	—

Adverse Events

Cetuximab + Irinotecan

Serious events: 3 serious events

Other events: 45 other events

Deaths: 3 deaths

Vemurafenib + Cetuximab + Irinotecan

Serious events: 25 serious events

Other events: 41 other events

Deaths: 4 deaths

Crossover: Vemurafenib + Cetuximab + Irinotecan

Serious events: 10 serious events

Other events: 21 other events

Deaths: 2 deaths

Serious adverse events

Measure	Cetuximab + Irinotecan n=46 participants at risk Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Vemurafenib + Cetuximab + Irinotecan n=46 participants at risk Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Crossover: Vemurafenib + Cetuximab + Irinotecan n=21 participants at risk Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Investigations Aspartate aminotransferase increased	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Blood and lymphatic system disorders Anemia	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Blood and lymphatic system disorders Febrile neutropenia	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Cardiac disorders Atrial flutter	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Cardiac disorders Cardiac disorders-Other	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Cardiac disorders Pericardial effusion	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Cardiac disorders Sinus tachycardia	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Abdominal pain	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Ascites	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Colitis	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Colonic obstruction	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Colonic perforation	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Constipation	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Diarrhea	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Duodenal hemorrhage	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Jejunal obstruction	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Nausea	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Pancreatitis	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Vomiting	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Death NOS	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Fatigue	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Fever	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Lung infection	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Sepsis	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Urinary tract infection	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Alanine aminotransferase increased	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Alkaline phosphatase increased	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Blood bilirubin increased	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Neutrophil count decreased	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations White blood cell decreased	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Anorexia	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Dehydration	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Renal and urinary disorders Acute kidney injury	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Renal and urinary disorders Renal calculi	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Vascular disorders Thromboembolic event	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.

Other adverse events

Measure	Cetuximab + Irinotecan n=46 participants at risk Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Vemurafenib + Cetuximab + Irinotecan n=46 participants at risk Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Crossover: Vemurafenib + Cetuximab + Irinotecan n=21 participants at risk Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	23.9% 11/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	45.7% 21/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	42.9% 9/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Eye disorders Blurred vision	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Eye disorders Conjunctivitis	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Eye disorders Eye disorders-Other	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Abdominal distension	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Abdominal pain	41.3% 19/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	39.1% 18/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	23.8% 5/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Colonic obstruction	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Constipation	23.9% 11/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Diarrhea	58.7% 27/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	60.9% 28/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	76.2% 16/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Dyspepsia	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Hemorrhoids	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Mucositis oral	15.2% 7/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	41.3% 19/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	23.8% 5/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Nausea	58.7% 27/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	58.7% 27/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	76.2% 16/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Vomiting	30.4% 14/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	45.7% 21/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	28.6% 6/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Edema limbs	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	17.4% 8/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Fatigue	67.4% 31/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	69.6% 32/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	76.2% 16/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Fever	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.6% 9/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Infusion related reaction	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Pain	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Urinary tract infection	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Injury, poisoning and procedural complications Bruising	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Injury, poisoning and procedural complications Fall	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Alanine aminotransferase increased	21.7% 10/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Alkaline phosphatase increased	23.9% 11/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	15.2% 7/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	33.3% 7/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Aspartate aminotransferase increased	26.1% 12/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	23.8% 5/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Blood bilirubin increased	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	15.2% 7/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Creatinine increased	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations INR increased	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Lymphocyte count decreased	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	14.3% 3/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Neutrophil count decreased	23.9% 11/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	43.5% 20/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	38.1% 8/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Platelet count decreased	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Weight loss	13.0% 6/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	28.3% 13/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	14.3% 3/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations White blood cell decreased	17.4% 8/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	32.6% 15/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	23.8% 5/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Anorexia	28.3% 13/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	30.4% 14/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	23.8% 5/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Dehydration	21.7% 10/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	23.8% 5/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hyperglycemia	13.0% 6/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hypoalbuminemia	23.9% 11/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	17.4% 8/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	33.3% 7/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hypocalcemia	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hypokalemia	26.1% 12/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	43.5% 20/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	28.6% 6/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hypomagnesemia	43.5% 20/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	26.1% 12/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	52.4% 11/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hyponatremia	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	21.7% 10/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Arthralgia	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	30.4% 14/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	33.3% 7/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Back pain	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tiss disorder - Other	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	14.3% 3/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	15.2% 7/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.6% 9/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Dizziness	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	13.0% 6/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Dysgeusia	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Headache	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Peripheral sensory neuropathy	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.6% 9/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	14.3% 3/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Psychiatric disorders Anxiety	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Psychiatric disorders Depression	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Psychiatric disorders Insomnia	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Renal and urinary disorders Hematuria	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Respiratory, thoracic and mediastinal disorders Cough	4.3% 2/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Respiratory, thoracic and mediastinal disorders Dyspnea	17.4% 8/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	15.2% 7/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Alopecia	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	32.6% 15/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Dry skin	19.6% 9/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	17.4% 8/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	14.3% 3/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	14.3% 3/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Photosensitivity	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	23.9% 11/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	19.0% 4/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Pruritus	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Rash acneiform	58.7% 27/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	47.8% 22/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	47.6% 10/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Rash maculo-papular	13.0% 6/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	28.3% 13/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	17.4% 8/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	2.2% 1/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	9.5% 2/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Vascular disorders Hot flashes	0.00% 0/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	6.5% 3/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Vascular disorders Hypertension	8.7% 4/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	10.9% 5/46 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	4.8% 1/21 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.

Additional Information

SWOG Statistician

SWOG Statistics & Data Management Center

Phone: 206-667-4408

Email: smcdonou@fredhutch.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place