Phase 2
N=106
S1406 Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer
Colorectal Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02164916 ↗Enrolled (actual)
106
Serious AEs
33.6%
Results posted
Oct 2017
Primary outcome: Primary: Progression-free Survival — 2.0; 4.3 months — p=0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- cetuximab (Biological); irinotecan hydrochloride (Drug); vemurafenib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- SWOG Cancer Research Network
- Primary completion
- Nov 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival |
2.0; 4.3 | 0.001 sig |
| SECONDARY Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug |
1; 2; 0; 2; 0; 1 | — |
Summary
This randomized phase II trial studies how well irinotecan hydrochloride and cetuximab with or without vemurafenib works in treating patients with colorectal cancer that has spread to nearby tissue or lymph nodes, that has spread to other places in the body, or cannot be removed by surgery. Irinotecan hydrochloride and vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may block the ability of tumor cells to grow and spread. It is not yet known whether irinotecan hydrochloride and cetuximab are more effective with or without vemurafenib in treating colorectal cancer.
Eligibility Criteria
- STEP I INITIAL REGISTRATION: BRAFV600E TESTING:
- Patients must have histologically or cytologically documented adenocarcinoma of the colon or rectum that is either metastatic, or locally advanced and unresectable
- Patients must have BRAFV600E mutant status documented by a Clinical Laboratory Improvements Amendments (CLIA) certified laboratory on a pathology report prior to Step 2 registration; use of an Food and Drug Administration (FDA)-approved test is preferred although other BRAF tests at a CLIA-certified laboratory may also be accepted; if a BRAFV600E mutation is known, then the patient must be registered to Step 2 Randomization immediately following Step 1 Initial Registration; if testing has not been performed locally, BRAFV600E testing must be completed by the central lab prior to Step 2 Randomization; if the specimen does not have a BRAFV600E mutation, the patient is ineligible for Step 2 Randomization
- Brain metastases are allowed if they have been adequately treated with radiotherapy or surgery and stable for at least 90 days prior to Step 1 Initial Registration; eligible patients should be neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to Step 1 Initial Registration
- Patients must have had one or two prior regimens of systemic chemotherapy for metastatic disease; prior treatment with irinotecan is allowed; a maintenance regimen of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted as a separate line of treatment; prior treatment for metastatic disease is not required for patients who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy
- Patients must not have been treated with any of the following prior to Step 2 Randomization:
- Cetuximab, panitumumab, or any other monoclonal antibody against EGFR or inhibitor of EGFR
- BRAF inhibitor including, but not limited to, vemurafenib or dabrafenib; regorafenib is not considered a BRAF inhibitor for the purpose of determining trial eligibility
- Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor including, but not limited to, trametinib or selumetinib
- Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at least 14 days prior to Step 1 Initial Registration and all toxicity must be resolved to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) grade 1 (with the exception of CTCAE v4.0 grade 2 neuropathy) prior to Step 1 Initial Registration
- Patients must not have a tumor with a mutation detected in codons 12 or 13 in KRAS; patients must not have a tumor with a known mutation detected in codons 61, 117, or 146 of KRAS or NRAS
- SPECIMEN SUBMISSION CRITERIA:
- Patients must have tumor (slides or block) available for submission for V600E BRAF testing
- Patients must have additional tumor available and be willing to submit tissue and blood samples
- SPECIMEN SUBMISSION CRITERIA REGULATORY CRITERIA:
- Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; for Step 1 Initial Registration of patients who have not yet submitted specimens for the central BRAFV600E testing, the appropriate consent form is the Step 1 Consent Form; for both Step 1 Initial Registration and Step 2 Randomization of patients whose BRAF mutation status is already known, the appropriate consent form is the Step 2 Consent Form
- STEP 2 RANDOMIZATION:
- Patients must have BRAFV600E mutation
- Patients must have measurable or non-measurable metastatic disease; computed tomography (CT) scans or magnetic resonance imaging (MRIs) used to assess all disease must have been completed within 28 days prior to Step 2 Randomization; CT scans or MRIs must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in S
Data sourced from ClinicalTrials.gov (NCT02164916). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.