Randomized Phase III Trial of mFOLFIRINOX vs. FOLFOX With Nivolumab for First-Line Treatment of Metastatic HER2- Gastroesophageal Adenocarcinoma
概览
- 阶段
- 3 期
- 干预措施
- Fluorouracil
- 疾病 / 适应症
- 未指定
- 发起方
- Alliance for Clinical Trials in Oncology
- 入组人数
- 382
- 试验地点
- 1561
- 主要终点
- Overall survival (OS)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
This phase III trial compares the effect of modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) for the treatment of advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The usual approach for patients is treatment with FOLFOX chemotherapy. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Fluorouracil stops cells from making DNA and it may kill tumor cells. Leucovorin is used with fluorouracil to enhance the effects of the drug. Oxaliplatin works by killing, stopping, or slowing the growth of tumor cells. Some patients also receive an immunotherapy drug, nivolumab, in addition to FOLFOX chemotherapy. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill tumor cells. Adding irinotecan to the FOLFOX regimen could shrink the cancer and extend the life of patients with advanced gastroesophageal cancers.
详细描述
PRIMARY OBJECTIVE: I. To determine if overall survival (OS) is improved in patients who received mFOLFIRINOX +/- nivolumab in comparison to FOLFOX +/- nivolumab as first-line chemotherapy for metastatic gastroesophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To compare other indices of efficacy, including progression-free survival, objective response rates and duration of response between both treatment arms. II. To evaluate safety and tolerability associated with treatment in each of the treatment arms. III. To evaluate the proportion of patients receiving second line of therapy in both arms. IV. To evaluate tolerability of the treatment in both arms using Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE). EXPLORATORY OBJECTIVES: I. Exploratory correlative markers will also be measured and evaluated within and between arms to better assess mechanisms and prognostic impact of markers on impact. These will include baseline PD-L1 combined positive score (CPS) and cell free deoxyribonucleic acid (cfDNA) before and after treatment. II. To evaluate and assess the feasibility and compliance associated with not centrally collecting perceived attribution of protocol treatment to reported adverse events. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive fluorouracil intravenously (IV), leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo magnetic resonance imaging (MRI) and a computed tomography (CT) scan throughout the trial. Patients may also undergo blood sample collection on study. ARM II: Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
研究者
入排标准
入选标准
- •Histologic documentation: HER2 negative adenocarcinoma as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines (Bartley et al., Journal of Clinical Oncology \[JCO\] 2017) with known PD-L1 CPS (Any CPS is allowed, but should be known prior to registration)
- •Stage: unresectable or metastatic
- •Tumor site: esophagus, gastroesophageal junction, or stomach
- •Measurable disease or non-measurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •No prior treatment for unresectable or metastatic disease
- •Prior neoadjuvant or adjuvant cytotoxic chemotherapy or adjuvant immunotherapy is allowed as long as it was completed at least 1 year prior to registration
- •Age \>= 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- •Absolute neutrophil count (ANC) \>= 1,500/mm\^3
- •Platelet count \>= 100,000/mm\^3
排除标准
- •Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
- •\* Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =\< 7 days prior to registration is required
- •No known Gilbert's syndrome or known homozygosity for UGAT1A1\*28 polymorphism
- •No baseline grade \>= 2 peripheral neuropathy, neurosensory toxicity, or neuromotor toxicity per CTCAE version (v) 5.0 regardless of causality
- •No medical condition such as uncontrolled infection or uncontrolled diabetes mellitus which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
- •No untreated, symptomatic brain metastasis. Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose for more than four weeks
- •No allogeneic tissue/organ transplant
研究组 & 干预措施
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Fluorouracil
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Leucovorin Calcium
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Oxaliplatin
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Irinotecan
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Nivolumab
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Magnetic Resonance Imaging
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Computed Tomography
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Biospecimen Collection
Arm I (mFOLFIRINOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Questionnaire Administration
Arm II (mFOLFOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Fluorouracil
Arm II (mFOLFOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Leucovorin Calcium
Arm II (mFOLFOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Oxaliplatin
Arm II (mFOLFOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Nivolumab
Arm II (mFOLFOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Magnetic Resonance Imaging
Arm II (mFOLFOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Computed Tomography
Arm II (mFOLFOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Biospecimen Collection
Arm II (mFOLFOX, nivolumab)
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
干预措施: Questionnaire Administration
结局指标
主要结局
Overall survival (OS)
时间窗: Up to 2 years from the time of randomization.
Will compare the distributions of OS between the two treatment arms to determine if patients treated with modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) (with or without nivolumab) have an OS benefit compared to those treated with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (with or without nivolumab). Kaplan-Meier methodology will be used to estimate the distributions for the treatment arms. To compare the OS distributions between the two treatment arms, we will use a one-sided logrank test to evaluate if mFOLFIRINOX (with or without nivolumab) is superior to mFOLFOX (with or without nivolumab) based on an intention to treat analysis. The hazard ratio, median OS, and estimated OS rates at 1 and 2 years will be estimated along with corresponding 95% confidence intervals. Multivariable Cox proportional hazards models will also be used to assess the impact of treatment arm on OS when stratifying on the stratification factors.
次要结局
- Patient reported outcomes(At baseline, day 1 of cycles 1-8 and day 1 of each odd-numbered cycle thereafter)
- Progression-free survival (PFS)(The time from registration to the time of documented progression and/or death, assessed up to 3 years)
- Overall response rate(Up to 3 years)
- Duration of Response(The time between each patient's best tumor response and progression (or date of last disease assessment for patients who die without progression or are lost to follow-up), assessed up to 3 years)
- Incidence of adverse events(Up to 3 years)