A study of patients with colorectal cancer that have a genetic abnormality in the BRAF gene taking encorafenib plus cetuximab with or without chemotherapy versus standard of care therapy
- Conditions
- Colorectal cancer (BRAF V600E-mutant mCRC)MedDRA version: 21.0Level: PTClassification code: 10061451Term: Colorectal cancer Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-509405-77-00
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 718
Molecular Prescreening Inclusion Criteria - Age and Sex: 1. SLI: Male or female participants age =18 years at the time of informed consent. Phase 3 and Cohort 3: Male or female participants age =16 years at the time of informed consent/assent in all countries where permitted. In countries or sites where enrollment of adolescents is not permitted (eg, Germany), male or female participants age =18 years at the time of informed consent. • Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants., 10. The Investigator must obtain prior to Cycle 1 Day 1 (SLI) or date of randomization (Phase 3 and Cohort 3) adequate tumor tissue (primary or metastatic, archival or newly obtained) for submission to a central laboratory for confirmation of BRAF V600E and tumor tissue assessment. Note: Once BRAF V600E mutation status is determined by the central laboratory (tumor tissue), the results will be considered definitive for eligibility. No repeat testing will be performed. Note: Lack of BRAF V600E confirmation by the central laboratory may be due to discordance between the local assay and central laboratory results (potential false positive local assay results), or due to inadequate or poor sample condition for central testing (indeterminate results). Note: Participants whose sample is determined to be inadequate or who have an indeterminate result on central testing may have additional tumor samples submitted for testing., 2. Body weight =40 kg., 3. Participants with histologically or cytologically confirmed colorectal adenocarcinoma., 4. Participants with evidence of Stage IV metastatic disease. Note: Patients with oligometastatic disease previously treated with curative intent are eligible to participate in the study as long as they have baseline measurable disease per RECIST 1.1. Oligometastatic colorectal cancer is characterized by a limited metastatic spread of disease. Oligometastatic disease is defined as the involvement of up to 3 sites with 5 or sometimes more metastases that for their anatomic localization is amenable to local therapies, thus rendering the patient free of disease., 5. Able to provide a sufficient amount of representative tumor specimen for central testing of BRAF V600E mutation status and tumor tissue assessment Note: Tumor sample can be archival or de novo (newly collected fixed biopsy sample) and must be in an FFPE block, or provide a minimum of 15 unstained slides of analyzable tissue. This tissue specimen should be obtained from a biopsy or surgery that was performed within 2 years prior to study enrollment. Participants with fewer than the required number of slides with analyzable tissue may be considered eligible if the Sponsor determines that the slides are sufficient for central testing., 6. Capable of giving signed informed consent/assent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Note: Participants =16 years old that are under guardianship may participate with the consent of their legally authorized guardian if permitted by local regulations. When appropriate, adolescent participants will be included in all discussions (see Section 10.1.3)., 7. Participants who have met all Molecular Prescreening inclusion criteria., 8. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study pro
Molecular Prescreening Exclusion Criteria Medical Conditions: 1. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study., Screening Exclusion Criteria Medical Conditions: 10. Impaired gastrointestinal function (eg, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, small bowel resection) or disease which may significantly alter the absorption of oral study intervention or recent changes in bowel function suggesting current or impending bowel obstruction., 11. Clinically significant cardiovascular diseases, including any of the following: a. History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) =6 months prior to randomization; b. Congestive heart failure requiring treatment (New York Heart Association Class II and above); c. Recent history (within 1 year prior to randomization) or presence of clinically significant cardiac arrhythmias (including uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); d. History of thromboembolic or cerebrovascular events =12 weeks prior to randomization. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (ie, massive or sub-massive) deep vein thrombosis or pulmonary emboli. Note: Participants with either deep vein thrombosis or pulmonary emboli that do not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of anticoagulants for at least 4 weeks. Note: Participants with thromboembolic events related to indwelling catheters (including PICC lines) or other procedures may be enrolled. e. Triplicate average QTcF interval =480 ms or a history of prolonged QT syndrome. Note: Participants with bundle-branch block (BBB) or with an implanted cardiac pacemaker, may enroll into the study following consultation with the Sponsor. f. Congenital LQTS., 12. Evidence of active noninfectious pneumonitis., 13. Evidence of active and uncontrolled bacterial or viral infection, with certain exceptions, as noted below, for chronic infection with HIV, hepatitis B or hepatitis C, within 2 weeks prior to start of study intervention., 14. Participants positive for HIV are ineligible unless they meet all of the following: a. A stable regimen of highly active anti-retroviral therapy that is not contraindicated (see Section 6.5); b. No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; c. A CD4 count >250 cells/mcL, and an undetectable HIV viral load on standard PCR-based tests., 2. Presence of acute or chronic pancreatitis., 3. Leptomeningeal disease., 4. History of chronic inflammatory bowel disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) =12 months prior to randomization., 5. Known DPD deficiency; refer to local fluorouracil or capecitabine label or local clinical guidances, for DPD status recommendation prior to starting treatment., 6. Gilbert's syndrome or known homozygous UGT1A1*28/*28 or UGT1A1*6/*6 genotypes or double heterozygous UGT1A1*6/*28 genotype: a. SLI: Participants with documented Gilbert's syndrome or known homozygous UGT1A1*28/*28 or UGT1A1*6/*6 ge
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method