NCT02164916|CompletedPhase 2ResultsDMC

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

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

SWOG Cancer Research Network ClinicalTrials.gov

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3 other identifiers

S1406U10CA180888NCI-2014-00814

Study Type

interventional

Target

106

Locations

1 country

Sites

763

Timeline

RegisteredJun 2014

StartedNov 2014

CompletionNov 2020

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

106

participants targeted

Target at P50-P75 for phase_2 colorectal-cancer

Timeline

Completed

Started Nov 2014

Longer than P75 for phase_2 colorectal-cancer

Geographic Reach

1 country

763 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.1 years study duration

First Submitted

Initial submission to the registry

June 13, 2014

Completed

4 days until next milestone

First Posted

Study publicly available on registry

June 17, 2014

Completed

5 months until next milestone

Study Start

First participant enrolled

November 1, 2014

Completed

3 years until next milestone

Results Posted

Study results publicly available

October 31, 2017

Completed

13 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 13, 2017

Completed

3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 19, 2020

Completed

Last Updated

December 30, 2020

Status Verified

December 1, 2020

Enrollment Period

3 years

First QC Date

June 13, 2014

Results QC Date

July 13, 2017

Last Update Submit

December 7, 2020

Conditions

Colorectal Cancer

Keywords

BRAF MutantMetastatic

Outcome Measures

Primary Outcomes (1)

Progression-free Survival
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.
Up to 3 years from randomization

Secondary Outcomes (1)

Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Up to 3 years

Other Outcomes (5)

Overall Survival
Up to 3 years from randomization
Overall Response Rate
Up to 3 years from randomization
Progression-free Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1
Up to 3 years from randomization
+2 more other outcomes

Study Arms (2)

Arm I (cetuximab, irinotecan hydrochloride)

ACTIVE COMPARATOR

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.

Biological: cetuximabDrug: irinotecan hydrochloride

Arm II (cetuximab, irinotecan hydrochloride, vemurafenib)

EXPERIMENTAL

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.

Biological: cetuximabDrug: irinotecan hydrochlorideDrug: vemurafenib

Interventions

cetuximabBIOLOGICAL

Given IV

Also known as: 11460, 205923-56-4, 3610, 714692, Anti-EGFR Monoclonal Antibody, Anti-Epidermal Growth Factor Receptor Monoclonal Antibody, C225, C225 monoclonal antibody, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225, Immunoglobulin G1, anti-(human epidermal growth factor receptor) (human-mouse monoclonal C225 gamma1-chain), disulfide with human-mouse monoclonal C225 kappa-chain, dimer, MOAB C225, monoclonal antibody C225

Arm I (cetuximab, irinotecan hydrochloride)Arm II (cetuximab, irinotecan hydrochloride, vemurafenib)

irinotecan hydrochlorideDRUG

Given IV

Also known as: Campto, Camptosar, camptothecin-11, CPT-11, irinotecan, irinotecan HCl, U-101440E

Arm I (cetuximab, irinotecan hydrochloride)Arm II (cetuximab, irinotecan hydrochloride, vemurafenib)

vemurafenibDRUG

Given PO

Also known as: BRAF(V600E) kinase inhibitor RO5185426, PLX4032, RG7204, RO5185426, Zelboraf

Arm II (cetuximab, irinotecan hydrochloride, vemurafenib)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

* 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 Solid Tumors \[RECIST\] 1.1) * Patients must have a Zubrod performance status of 0-1 * Absolute neutrophil count (ANC) \>= 1,500/mcL * Platelets \>= 100,00/mcL * Hemoglobin \>= 9 g/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal (IULN) or =\< 5 x IULN if liver metastases are present * Total bilirubin =\< 1.5 x IULN * Serum creatinine =\< 1.5 x IULN within 14 days prior to Step 2 Randomization OR * Calculated creatinine clearance \> 60 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to Step 2 Randomization * Patients must have an electrocardiogram (ECG) within 14 days prior to Step 2 Randomization * Patients must have corrected QT (QTc) =\< 500 msec * Patients must not have a known history of Gilbert's Syndrome or known homozygosity for the UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)\*28 allele * Patients must not have interstitial pneumonia or extensive symptomatic interstitial fibrosis of the lung * Patients must not have an uncontrolled intercurrent illness including, but not limited to, active bleeding diathesis, uncontrolled infection/disorders, nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy, or psychiatric illness/social situations which would limit compliance with study requirements * Patients must be able to swallow pill/tablet and have no refractory nausea, vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption * Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method while on study and for 30 days after study treatment; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures, he/she is responsible for beginning contraceptive measures * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years * STEP 2 RANDOMIZATION 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 all patients, the appropriate consent form for this registration is the Step 2 Consent Form * As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * STEP 3 CROSSOVER REGISTRATION: * Patients must have documented disease progression while on Arm 1 of this protocol; the follow-up tumor assessment form documenting disease progression must be submitted to Southwestern Oncology Group (SWOG) prior to Step 3 * Registration to Step 3 Crossover must be within 28 days of discontinuation of Arm 1 protocol treatment; patients going off treatment for any other reason are not eligible * ANC \>= 1,500/mcL within 14 days prior to Step 3 registration * Platelets \>= 100,00/mcL within 14 days prior to Step 3 registration * Hemoglobin \>= 9 g/dL within 14 days prior to Step 3 registration * AST and ALT =\< 2.5 x institutional upper limit of normal (IULN) or =\< 5 x IULN if liver metastases are present within 14 days prior to Step 3 registration * Total bilirubin =\< 1.5 x IULN within 14 days prior to Step 3 registration * Serum creatinine =\< 1.5 x IULN within 14 days prior to Step 3 registration OR * Calculated creatinine clearance \> 60 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to Step 3 registration

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

SWOG Cancer Research Networklead
National Cancer Institute (NCI)collaborator
Roche-Genentechcollaborator

Study Sites (763)

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC