Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation
Metastatic Colon Adenocarcinoma, Metastatic Rectal Adenocarcinoma, Stage III Colon Cancer AJCC v8
About this trial
This is an interventional treatment trial for Metastatic Colon Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
- Participants must have a histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum. The date of diagnosis will be determined according to the pathologic date of diagnosis
- Participants must have measurable disease according to RECIST1.1 criteria. Computed tomography (CT) scans or magnetic resonance imaging (MRIs) used to assess measurable disease must have been completed within 28 days prior to registration. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form
- Participants must have documented unresectable and/or metastatic disease on CT or MRI imaging. All disease must be assessed and documented on the Baseline Tumor Assessment Form
- Participants must have BRAF^V600E mutated colorectal cancer as tested in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
- Participants must have proficient mismatch repair (pMMR) or microsatellite stable (MSS) status as tested in a CLIA-certified laboratory and documented by the treating clinician. Proficient mismatch repair status can be determined by intact expression by immunohistochemistry of all 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). Microsatellite instability can be determined by polymerase chain reaction (PCR)
- Participants with brain metastases must have completed surgery or radiation therapy >= 28 days prior to registration. These participants must have a CT or MRI of the brain showing no new or enlarging lesions within 42 days prior to registration. These participants must also be neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to registration. Metastatic brain parenchymal disease must have been treated and participant must be off steroids for 7 days prior to registration. The presence of leptomeningeal disease (LMD) is not considered stable disease, and participants with LMD are not eligible for this study
- Participants with known evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration
- Participants must have had one or two prior regimens of systemic chemotherapy for metastatic or locally advanced, unresectable disease. (A maintenance regimen of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted as a separate line of treatment. The re-introduction of an initially successful induction regimen will not be counted as one additional 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
- Participants must be of age >= 18 years at the time of informed consent
- Participants must have a Zubrod performance status of 0 or 1
- Participants must have a complete medical history and physical exam within 28 days prior to registration
- Absolute neutrophil count >= 1.0 x 10^3/uL (within 28 days prior to registration)
- Hemoglobin >= 9 g/dL (within 28 days prior to registration)
- Platelets >= 75 x 10^3/uL (within 28 days prior to registration)
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to registration)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to registration)
- If liver metastases are present, then it is acceptable for AST level =< 5.0 x ULN, and/or an ALT level =< 5.0 x ULN (within 28 days prior to registration)
- Participants must have serum creatinine =< the IULN OR measured OR calculated creatinine clearance >= 50 mL/min using the Cockroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
- Participants must be able to swallow and retain pills
- Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better
- Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
- Note: 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
Exclusion Criteria:
- Participants must not have a known positive serology for human immunodeficiency virus (HIV). Encorafenib is contraindicated with concomitant use of non-nucleoside analog reverse transcriptase inhibitors like efavirenz and etravirine. In addition, it is recommended in the investigator brochure of encorafenib to avoid using encorafenib with protease inhibitors. Therefore, because all participants on this study would receive encorafenib for either randomized arm of treatment, participants with HIV who receive these components of highly active antiretroviral therapy (HAART) would be at high risk for complications of drug-drug interaction
- Participants must not have had prior treatment with a BRAF inhibitor (including, but not limited to, encorafenib, dabrafenib, or vemurafenib), MEK inhibitor (including, but not limited to, trametinib, selumetinib, or binimetinib), or ERK inhibitor (of note, regorafenib is not considered a BRAF inhibitor for the context of eligibility criteria)
- Participants must not have had prior treatment with anti-EGFR therapies
- Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Participants must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as long as there has been a washout period for corticosteroids of >= 7 days prior to registration
- Participants must not have received a live vaccine within 30 days prior to study registration. Seasonal flu and COVID vaccines that do not contain a live virus are permitted
- Participants must not be receiving any other investigational agents
- Participants must not have impaired gastrointestinal function or disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
Participants must not have a history of inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis).
- Note: Participants with Graves' disease will be allowed
- Participants must not have a history of pneumonitis that has required oral or intravenous (IV) steroids within the last 12 months
- Participants must not have a history of a grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy
- Participants must not have a history of a prior allogeneic tissue or solid organ transplant
- Participants must not have a history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) within 6 months prior to study registration
Participants must not have uncontrolled blood pressure and hypertension within 28 days prior to registration.
- Uncontrolled blood pressure and hypertension is defined as systolic blood pressure (SBP) > 170 mmHg or diastolic blood pressure (DBP) > 100 mmHg within 28 days prior to registration. Participants are permitted to be receiving multiple anti-hypertensive medications (unless otherwise indicated in the study). All blood pressure measurements within the 28 days prior to registration must be SBP =< 170 and DBP =< 100. An exception can be made by a healthcare provider for a participant with a single blood pressure elevation who upon rechecking has a normal blood pressure
- Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen or requires concurrent therapy
- Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion and vasectomy with testing showing no sperm in the semen
- Participants must not be planning treatment with other systemic anti-cancer agents (e.g., chemotherapy, hormonal therapy, immunotherapy) or other treatments not part of protocol-specified anti-cancer therapy including concurrent investigational agents of any type
Sites / Locations
- CTCA at Western Regional Medical CenterRecruiting
- Kaiser Permanente DublinRecruiting
- Kaiser Permanente-FremontRecruiting
- Kaiser Permanente-FresnoRecruiting
- Kaiser Permanente-ModestoRecruiting
- Kaiser Permanente-OaklandRecruiting
- UC Irvine Health/Chao Family Comprehensive Cancer CenterRecruiting
- Kaiser Permanente-RosevilleRecruiting
- Kaiser Permanente Downtown CommonsRecruiting
- Kaiser Permanente-South SacramentoRecruiting
- Kaiser Permanente-San FranciscoRecruiting
- Kaiser Permanente-Santa Teresa-San JoseRecruiting
- Kaiser Permanente San LeandroRecruiting
- Kaiser Permanente Medical Center - Santa ClaraRecruiting
- Kaiser Permanente-Santa RosaRecruiting
- Kaiser Permanente-South San FranciscoRecruiting
- Kaiser Permanente-VallejoRecruiting
- Kaiser Permanente-Walnut CreekRecruiting
- UCHealth University of Colorado HospitalRecruiting
- UCHealth Memorial Hospital CentralRecruiting
- Memorial Hospital NorthRecruiting
- Poudre Valley HospitalRecruiting
- Cancer Care and Hematology-Fort CollinsRecruiting
- UCHealth Greeley HospitalRecruiting
- UCHealth Highlands Ranch HospitalRecruiting
- Medical Center of the RockiesRecruiting
- CTCA at Southeastern Regional Medical CenterRecruiting
- Kaiser Permanente Moanalua Medical CenterRecruiting
- Saint Alphonsus Cancer Care Center-BoiseRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Saint Alphonsus Cancer Care Center-CaldwellRecruiting
- Kootenai Health - Coeur d'AleneRecruiting
- Saint Luke's Cancer Institute - FruitlandRecruiting
- Saint Luke's Cancer Institute - MeridianRecruiting
- Saint Luke's Cancer Institute - NampaRecruiting
- Saint Alphonsus Cancer Care Center-NampaRecruiting
- Kootenai Clinic Cancer Services - Post FallsRecruiting
- Kootenai Cancer ClinicRecruiting
- Saint Luke's Cancer Institute - Twin FallsRecruiting
- Rush - Copley Medical CenterRecruiting
- Advocate Good Shepherd HospitalRecruiting
- Illinois CancerCare-BloomingtonRecruiting
- Illinois CancerCare-CantonRecruiting
- Illinois CancerCare-CarthageRecruiting
- Centralia Oncology ClinicRecruiting
- Advocate Illinois Masonic Medical CenterRecruiting
- AMG Crystal Lake - OncologyRecruiting
- Carle at The RiverfrontRecruiting
- Cancer Care Specialists of Illinois - DecaturRecruiting
- Decatur Memorial HospitalRecruiting
- Illinois CancerCare-DixonRecruiting
- Advocate Good Samaritan HospitalRecruiting
- Carle Physician Group-EffinghamRecruiting
- Crossroads Cancer CenterRecruiting
- Advocate Sherman HospitalRecruiting
- Illinois CancerCare-EurekaRecruiting
- Illinois CancerCare-GalesburgRecruiting
- Advocate South Suburban HospitalRecruiting
- Illinois CancerCare-Kewanee ClinicRecruiting
- AMG Libertyville - OncologyRecruiting
- Condell Memorial HospitalRecruiting
- Illinois CancerCare-MacombRecruiting
- Carle Physician Group-Mattoon/CharlestonRecruiting
- Cancer Care Center of O'FallonRecruiting
- Advocate Christ Medical CenterRecruiting
- Illinois CancerCare-Ottawa ClinicRecruiting
- Advocate Lutheran General HospitalRecruiting
- Illinois CancerCare-PekinRecruiting
- Illinois CancerCare-PeoriaRecruiting
- Illinois CancerCare-PeruRecruiting
- Illinois CancerCare-PrincetonRecruiting
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Carle Cancer CenterRecruiting
- Illinois CancerCare - WashingtonRecruiting
- Rush-Copley Healthcare CenterRecruiting
- Northwest Cancer Center - Main CampusRecruiting
- Northwest Oncology LLCRecruiting
- Northwest Cancer Center - HobartRecruiting
- Saint Mary Medical CenterRecruiting
- Franciscan Health IndianapolisRecruiting
- Saint Catherine HospitalRecruiting
- Franciscan Saint Elizabeth Health - Lafayette EastRecruiting
- Woodland Cancer Care Center
- Franciscan Health MooresvilleRecruiting
- The Community HospitalRecruiting
- Women's Diagnostic Center - MunsterRecruiting
- Northwest Cancer Center - ValparaisoRecruiting
- Mary Greeley Medical CenterRecruiting
- McFarland Clinic - AmesRecruiting
- McFarland Clinic - BooneRecruiting
- Mercy Medical Center - Des MoinesRecruiting
- McFarland Clinic - Trinity Cancer CenterRecruiting
- McFarland Clinic - JeffersonRecruiting
- McFarland Clinic - MarshalltownRecruiting
- LSU Health Baton Rouge-North ClinicRecruiting
- Ochsner Hematology Oncology North Shore - Covington (West Region)Recruiting
- Ochsner Medical Center JeffersonRecruiting
- Saint Joseph Mercy HospitalRecruiting
- Bronson Battle CreekRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
- Saint Joseph Mercy CantonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
- Saint Joseph Mercy ChelseaRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
- Ascension Saint John HospitalRecruiting
- Great Lakes Cancer Management Specialists-Doctors ParkRecruiting
- Genesee Cancer and Blood Disease Treatment CenterRecruiting
- Genesee Hematology Oncology PCRecruiting
- Genesys Hurley Cancer InstituteRecruiting
- Hurley Medical CenterRecruiting
- Spectrum Health at Butterworth CampusRecruiting
- Trinity Health Grand Rapids HospitalRecruiting
- Academic Hematology Oncology SpecialistsRecruiting
- Great Lakes Cancer Management Specialists-Van Elslander Cancer CenterRecruiting
- Bronson Methodist HospitalRecruiting
- West Michigan Cancer CenterRecruiting
- Ascension Borgess Cancer CenterRecruiting
- Sparrow HospitalRecruiting
- Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
- Great Lakes Cancer Management Specialists-Macomb Medical CampusRecruiting
- Trinity Health Muskegon HospitalRecruiting
- Cancer and Hematology Centers of Western Michigan - Norton ShoresRecruiting
- Ascension Providence Hospitals - Novi
- Spectrum Health Reed City HospitalRecruiting
- Marie Yeager Cancer CenterRecruiting
- Ascension Providence Hospitals - Southfield
- Bhadresh Nayak MD PC-Sterling HeightsRecruiting
- Munson Medical CenterRecruiting
- Great Lakes Cancer Management Specialists-Macomb Professional BuildingRecruiting
- Macomb Hematology Oncology PCRecruiting
- Saint John Macomb-Oakland HospitalRecruiting
- University of Michigan Health - WestRecruiting
- Huron Gastroenterology PCRecruiting
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
- Mercy HospitalRecruiting
- Essentia Health - Deer River ClinicRecruiting
- Essentia Health Cancer CenterRecruiting
- Fairview Southdale HospitalRecruiting
- Essentia Health Hibbing ClinicRecruiting
- Abbott-Northwestern HospitalRecruiting
- North Memorial Medical Health CenterRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- Regions HospitalRecruiting
- United HospitalRecruiting
- Essentia Health SandstoneRecruiting
- Essentia Health Virginia ClinicRecruiting
- Saint Francis Medical CenterRecruiting
- Community Hospital of AnacondaRecruiting
- Billings Clinic Cancer CenterRecruiting
- Bozeman Deaconess HospitalRecruiting
- Benefis Healthcare- Sletten Cancer InstituteRecruiting
- Kalispell Regional Medical CenterRecruiting
- Community Medical HospitalRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Roswell Park Cancer InstituteRecruiting
- Southeastern Medical Oncology Center-ClintonRecruiting
- Southeastern Medical Oncology Center-GoldsboroRecruiting
- Southeastern Medical Oncology Center-JacksonvilleRecruiting
- FirstHealth of the Carolinas-Moore Regional HospitalRecruiting
- Strecker Cancer Center-BelpreRecruiting
- Miami Valley Hospital SouthRecruiting
- Adena Regional Medical CenterRecruiting
- Mount Carmel East HospitalRecruiting
- Columbus Oncology and Hematology Associates IncRecruiting
- Riverside Methodist HospitalRecruiting
- Grant Medical CenterRecruiting
- The Mark H Zangmeister CenterRecruiting
- Doctors HospitalRecruiting
- Dayton Blood and Cancer CenterRecruiting
- Miami Valley HospitalRecruiting
- Dayton Physician LLC-Miami Valley Hospital NorthRecruiting
- Miami Valley Hospital NorthRecruiting
- Delaware Health Center-Grady Cancer CenterRecruiting
- Grady Memorial HospitalRecruiting
- Columbus Oncology and Hematology AssociatesRecruiting
- Atrium Medical Center-Middletown Regional HospitalRecruiting
- Dayton Physicians LLC-AtriumRecruiting
- Mount Carmel Grove City HospitalRecruiting
- Kettering Medical CenterRecruiting
- Fairfield Medical CenterRecruiting
- OhioHealth Mansfield HospitalRecruiting
- OhioHealth Marion General HospitalRecruiting
- Knox Community HospitalRecruiting
- Licking Memorial HospitalRecruiting
- Southern Ohio Medical CenterRecruiting
- Springfield Regional Cancer CenterRecruiting
- Springfield Regional Medical CenterRecruiting
- Toledo Clinic Cancer Centers-ToledoRecruiting
- Upper Valley Medical CenterRecruiting
- Saint Ann's HospitalRecruiting
- Genesis Healthcare System Cancer Care CenterRecruiting
- Cancer Centers of Southwest Oklahoma ResearchRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Mercy Hospital Oklahoma CityRecruiting
- Clackamas Radiation Oncology CenterRecruiting
- Providence Cancer Institute Clackamas ClinicRecruiting
- Providence Newberg Medical CenterRecruiting
- Saint Alphonsus Medical Center-OntarioRecruiting
- Providence Willamette Falls Medical CenterRecruiting
- Providence Portland Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Lehigh Valley Hospital - MuhlenbergRecruiting
- University of Pennsylvania/Abramson Cancer CenterRecruiting
- Rhode Island HospitalRecruiting
- Prisma Health Cancer Institute - SpartanburgRecruiting
- Medical University of South CarolinaRecruiting
- Prisma Health Cancer Institute - EasleyRecruiting
- Prisma Health Cancer Institute - ButternutRecruiting
- Prisma Health Cancer Institute - FarisRecruiting
- Prisma Health Greenville Memorial HospitalRecruiting
- Prisma Health Cancer Institute - EastsideRecruiting
- Prisma Health Cancer Institute - GreerRecruiting
- Prisma Health Cancer Institute - SenecaRecruiting
- Vanderbilt University/Ingram Cancer CenterRecruiting
- The Don and Sybil Harrington Cancer CenterRecruiting
- M D Anderson Cancer CenterRecruiting
- Huntsman Cancer Institute/University of UtahRecruiting
- Norris Cotton Cancer Center-NorthRecruiting
- Swedish Cancer Institute-IssaquahRecruiting
- Swedish Medical Center-First HillRecruiting
- West Virginia University HealthcareRecruiting
- ThedaCare Regional Cancer CenterRecruiting
- Duluth Clinic AshlandRecruiting
- Marshfield Medical Center-EC Cancer CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Marshfield Clinic-Minocqua CenterRecruiting
- ProHealth D N Greenwald CenterRecruiting
- ProHealth Oconomowoc Memorial HospitalRecruiting
- Marshfield Medical Center-River Region at Stevens PointRecruiting
- UW Cancer Center at ProHealth CareRecruiting
- Marshfield Medical Center - WestonRecruiting
- Centro Comprensivo de Cancer de UPRRecruiting
- PROncologyRecruiting
- San Juan City HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I (encorafenib, cetuximab, nivolumab)
Arm II (encorafenib, cetuximab)
Patients receive encorafenib PO QD on days 1-28, cetuximab IV on days 1 and 15, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive encorafenib PO QD on days 1-28 and cetuximab IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.