A Multi-Centre Randomised Clinical Trial of Biomarker-Driven Maintenance Treatment for First-Line Metastatic Colorectal Cancer (MODUL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,044
- 试验地点
- 154
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This randomized, multi-center, active-controlled, open-label, parallel-group study will investigate the efficacy and safety of biomarker-driven maintenance treatment for first-line mCRC. Participants with mCRC are eligible for entry and cannot have received any prior chemotherapy in the metastatic setting. The entire study duration is anticipated to be approximately 7.5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG PS of less than or equal to (<=) 2
- •At least 16 weeks of life expectancy at time of entry into the study
- •Histologically confirmed colorectal cancer (CRC) with mCRC confirmed radiologically
- •Measureable, unresectable disease according to RECIST 1.1
- •No prior chemotherapy for CRC in the metastatic setting
- •Archival tumor formalin-fixed paraffin-embedded tissue block from the primary tumor obtained at the time of the initial diagnosis is available
- •Adequate hematological, liver and renal function
- •Agreement to use highly effective measures of contraception
- •Exclusion Criteria for All Participants:
- •Less than 6 months from completion of any prior neoadjuvant or adjuvant chemotherapy, radiotherapy
- •Prior or current treatment with bevacizumab or any other anti-angiogenic drug (vascular endothelial growth factor or vascular endothelial growth factor receptor therapies or tyrosine kinase inhibitors)
- •Current or recent (within 10 days of study enrollment) use of aspirin (more than [>] 325 milligrams per day [mg/day]), clopidogrel (> 75 mg/day), or current or recent (within 10 days prior to the start of study induction treatment) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic uses allowed)
- •Active infection requiring intravenous antibiotics at the start of study induction treatment
- •Previous or concurrent malignancy, except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the participant has been disease-free for 5 years prior to study entry
- •Inadequately controlled hypertension; prior history of hypertensive crisis or hypertensive encephalopathy
- •Clinically significant (active) cardiovascular disease, for example cerebrovascular accidents <= 6 months prior to start of study induction treatment, myocardial infarction <= 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Functional Classification Grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
- •Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of start of study induction treatment
- •Active symptomatic or untreated central nervous system (CNS) metastases; CNS disease other than supratentorial or cerebellar metastases (in other words, patients with metastases to midbrain, pons, medulla or spinal cord are excluded); history of or known carcinomatous meningitis
- •Known hypersensitivity to any component of any of the study induction or maintenance treatment medications
- •Pregnancy or lactation
- •Exclusion Criteria for Participants in Cohort 1 (MP):
- •Inability to swallow pills
- •Refractory nausea and vomiting, malabsorption, external biliary shunt or significant bowel resection that would preclude adequate absorption
- •History or presence of clinically significant ventricular or atrial dysrhythmias
- •Corrected QT (QTc) interval >= 450 millisecond assessed within 3 weeks prior to randomization, long QT syndrome or, uncorrectable electrolyte abnormalities (including magnesium) or requirement for medicinal products known to prolong the QT interval
- •ECOG PS > 2
- •Exclusion Criteria for Participants in Cohort 2 (MP):
- •History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
- •Prior allogeneic bone marrow transplantation or prior solid organ transplantation
- •History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis at most recent chest imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI])
- •Positive test for human immunodeficiency virus (HIV)
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) at Screening
- •Active tuberculosis
- •Severe infection within 4 weeks prior to start of maintenance treatment including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia; has signs or symptoms of significant infection or has received oral or IV antibiotics within 2 weeks prior to start of maintenance treatment
- •Administration of a live, attenuated vaccine within 4 weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study
- •Prior treatment with cluster of differentiation (CD) 137 agonists, anti-cytotoxic T-lymphocyte-associated antigen (CTLA) 4, anti-programmed death-1 (PD-1), or anti-programmed death-ligand 1 (PD-L1) therapeutic antibody or pathway-targeting agents
- •Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of maintenance treatment
- •Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of maintenance treatment, or anticipated requirement for systemic immunosuppressive medications during the remainder of the study
- •If receiving receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (for example, denosumab) and unwilling to adopt alternative treatment such as bisphosphonates while receiving atezolizumab
- •Exclusion Criteria for Participants in Cohort 3 (MP):
- •Inability to swallow pills
- •Left ventricular ejection fraction (LVEF) less than (<) 50 percent (%) as assessed after completion of induction treatment by either 2-dimensional echocardiogram or multiple-gated acquisition
- •Clinically significant cardiovascular disease, including unstable angina, history of or active congestive heart failure of ≥ NYHA Grade 2, history of or ongoing serious cardiac arrhythmia requiring treatment (except for controlled atrial fibrillation and/or paroxysmal supraventricular tachycardia).
- •Current uncontrolled hypertension with or without medication
- •Current dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy
- •Insulin-dependent diabetes
- •Current known infection with HIV, HBV, or HCV (active infection or carriers)
- •Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
- •Known hypersensitivity to murine proteins
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排除标准
- 未提供
研究组 & 干预措施
Cohort 1: Induction Phase (IP)
Includes participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: FOLFOX induction regimen (Drug)
Cohort 1: Induction Phase (IP)
Includes participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: Bevacizumab (Drug)
Cohort 4 (IP)
Includes participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: FOLFOX induction regimen (Drug)
Cohort 1: Induction Phase (IP)
Includes participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: 5-FU/LV (Drug)
Cohort 2 (IP)
Includes participants with BRAFwt. All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: FOLFOX induction regimen (Drug)
Cohort 2 (IP)
Includes participants with BRAFwt. All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: Bevacizumab (Drug)
Cohort 2 (IP)
Includes participants with BRAFwt. All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: 5-FU/LV (Drug)
Cohort 3 (IP)
Includes participants with human epidermal growth factor receptor 2 positive (HER2+). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: FOLFOX induction regimen (Drug)
Cohort 3 (IP)
Includes participants with human epidermal growth factor receptor 2 positive (HER2+). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: Bevacizumab (Drug)
Cohort 3 (IP)
Includes participants with human epidermal growth factor receptor 2 positive (HER2+). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: 5-FU/LV (Drug)
Cohort 4 (IP)
Includes participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: Bevacizumab (Drug)
Cohort 4 (IP)
Includes participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
干预措施: 5-FU/LV (Drug)
Cohort 1 (Maintenance Phase[MP]):5-FU/LV,cetuximab,vemurafenib
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) will receive 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
干预措施: Cetuximab (Drug)
Cohort 1 (Maintenance Phase[MP]):5-FU/LV,cetuximab,vemurafenib
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) will receive 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
干预措施: Vemurafenib (Drug)
Cohort 1 (Maintenance Phase[MP]):5-FU/LV,cetuximab,vemurafenib
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) will receive 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
干预措施: 5-FU/LV (Drug)
Cohort 1 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
干预措施: Fluoropyrimidine (5-FU/LV or capecitabine) (Drug)
Cohort 1 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
干预措施: Bevacizumab (Drug)
Cohort 2 (MP):5-FU/LV or capecitabine,bevacizumab,atezolizumab
Participants with BRAFwt will receive fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
干预措施: Fluoropyrimidine (5-FU/LV or capecitabine) (Drug)
Cohort 2 (MP):5-FU/LV or capecitabine,bevacizumab,atezolizumab
Participants with BRAFwt will receive fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
干预措施: Atezolizumab (Drug)
Cohort 2 (MP):5-FU/LV or capecitabine,bevacizumab,atezolizumab
Participants with BRAFwt will receive fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
干预措施: Bevacizumab (Drug)
Cohort 2 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
干预措施: Fluoropyrimidine (5-FU/LV or capecitabine) (Drug)
Cohort 2 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
干预措施: Bevacizumab (Drug)
Cohort 3 (MP): capecitabine,trastuzumab,pertuzumab
Participants with human epidermal growth factor receptor 2 positive (HER2+) will receive 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
干预措施: Trastuzumab (Drug)
Cohort 3 (MP): capecitabine,trastuzumab,pertuzumab
Participants with human epidermal growth factor receptor 2 positive (HER2+) will receive 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
干预措施: Pertuzumab (Drug)
Cohort 3 (MP): capecitabine,trastuzumab,pertuzumab
Participants with human epidermal growth factor receptor 2 positive (HER2+) will receive 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
干预措施: Capecitabine (Drug)
Cohort 3 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
干预措施: Fluoropyrimidine (5-FU/LV or capecitabine) (Drug)
Cohort 3 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
干预措施: Bevacizumab (Drug)
Cohort 4 (MP): Cobimetinib,atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) will receive 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
干预措施: Atezolizumab (Drug)
Cohort 4 (MP): Cobimetinib,atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) will receive 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
干预措施: Cobimetinib (Drug)
Cohort 4 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
干预措施: Fluoropyrimidine (5-FU/LV or capecitabine) (Drug)
Cohort 4 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
干预措施: Bevacizumab (Drug)
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment will have the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor is MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor is MSI-H. This cohort will be followed for adverse events during the study, but is not part of the Maintenance Phase study objectives.
干预措施: Cetuximab (Drug)
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment will have the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor is MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor is MSI-H. This cohort will be followed for adverse events during the study, but is not part of the Maintenance Phase study objectives.
干预措施: Fluoropyrimidine (5-FU/LV or capecitabine) (Drug)
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment will have the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor is MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor is MSI-H. This cohort will be followed for adverse events during the study, but is not part of the Maintenance Phase study objectives.
干预措施: Atezolizumab (Drug)
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment will have the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor is MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor is MSI-H. This cohort will be followed for adverse events during the study, but is not part of the Maintenance Phase study objectives.
干预措施: Vemurafenib (Drug)
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment will have the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor is MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor is MSI-H. This cohort will be followed for adverse events during the study, but is not part of the Maintenance Phase study objectives.
干预措施: Bevacizumab (Drug)
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment will have the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor is MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor is MSI-H. This cohort will be followed for adverse events during the study, but is not part of the Maintenance Phase study objectives.
干预措施: 5-FU/LV (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From randomization until disease progression or death from any cause, up to 5 years
PFS is defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
次要结局
- Time to Treatment Response(From randomization until disease progression or death from any cause, up to 5 years)
- Overall Survival (OS)(From randomization until death from any cause, up to 5 years)
- Overall Response(From randomization until disease progression, up to 5 years)
- Disease Control Rate (DCR)(From randomization until disease progression, up to 5 years)
- Duration of Response(From first objective response until disease progression or death from any cause, up to 5 years)
- Percentage of Participants With Adverse Events(From baseline until end of study (up to 5 years))
- Percentage of Participants With Improvement and/or Stayed the Same on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score(From baseline until end of study (up to 5 years))