Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab Versus mFOLFOX6 + Panitumumab in Metastatic Colorectal Cancer Patients Selected by RAS and B-RAF Status From Circulating DNA Analysis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- UNICANCER
- 入组人数
- 219
- 试验地点
- 6
- 主要终点
- Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.
研究概览
简要总结
National trial, multicenter, randomized, phase II assessing FOLFIRINOX + Panitumumab versus mFOLFOX6 + Panitumumab in metastatic colorectal cancer patients selected by RAS and B-RAF status from circulating DNA analysis.
Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.
详细描述
PRIMARY OBJECTIVE: Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab
SECONDARY OBJECTIVE(S):
- Overall Survival
- Progression free survival
- Secondary resection
- Early tumor shrinkage (ETS)
- Depth of response (DpR)
- Safety profile (NCI-CTCAE v4.03 classification)
- Diagnostic performance of ccfDNA analysis compared to the tumor-tissue analysis (current gold standard)
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
盲法说明
The primary endpoint is the complete response rate where complete response is defined as complete disappearance of metastatic lesions after a maximum of 12 cycles of chemotherapy and tumor marker level normalization (CEA).
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 75 years
- •ECOG PS between 0 and 1
- •Histologically confirmed adenocarcinoma of the colon or rectum
- •Untreated synchronous or metachronous metastatic disease deemed unresectable with curative intent
- •K-Ras (codons 12, 13, 59, 61, 117, 146), N-Ras (codons 12, 13, 59, 61) and B-Raf (codon 600) wild-type tumor status according to plasma analysis of circulating cell free DNA by Intplex technology
- •Measurable disease according to RECIST version 1.1
- •Adequate hematologic, hepatic and renal functions:
- •Absolute neutrophil count (ANC) ≥2 x 109/L
- •Haemoglobin ≥9 g/dL
- •Platelets (PTL) ≥100 x 109/L
- •AST/ALT ≤5 x ULN
- •Alkaline phosphatase ≤2.5 x ULN
- •Bilirubin ≤1.5 x ULN
- •Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula)
- •Life expectancy of at least 3 months
- •Adequate contraception if applicable
- •Patient affiliated to a social security regimen
- •Patient information and signed written consent form
- •Uracilemia < 16 ng/ml
排除标准
- •History of other malignancy within the previous 5 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)
- •Adjuvant treatment with oxaliplatin
- •Previous treatment for metastatic disease
- •Patients who received any chemo- and/or radiotherapy within 15 days from the date of blood sampling for the RAS and BRAF test
- •Brain metastases
- •Patients with a history of severe or life-threatening hypersensitivity to the active substances or to any of the excipients delivered in this study
- •Patient with history of pulmonary fibrosis or interstitial pneumonitis
- •Previous organ transplantation, HIV or other immunodeficiency syndromes
- •Concomitant medications/comorbidities that may prevent the patient from receiving study treatment as uncontrolled intercurrent illness (for instance: active infection, active inflammatory disorders, inflammatory bowel disease, intestinal obstruction, symptomatic congestive heart failure, uncontrolled hypertension...)
- •Persistent peripheral neuropathy >grade1 (NCI CT v4.03)
- •Ionic disorders as:
- •Kalemia ≤1 x LLN
- •Magnesemia <0.5mmol/L
- •Calcemia <2mmol/L
- •Patient with known dihydropyrimidine dehydrogenase deficiency
- •QT/QTc>450msec for men and >470msec for women
- •Patient with contraindication for trial drugs (investigators have to refer to SmPC drugs, see Appendix 7)
- •Concomitant intake of St. John's wort
- •Other concomitant cancer
- •Participation in another therapeutic trial
- •Pregnant woman or lactating woman
- •Patients with psychological, familial, sociological or geographical condition hampering compliance with the study protocol and follow-up schedule
- •Legal incapacity or limited legal capacity
研究组 & 干预措施
A=Experimental group
FOLFIRINOX + Panitumumab oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² given as a 2-hour intravenous (IV) infusion with the addition, after 30 minutes of irinotecan 150 mg/m² given as a 90-minute intravenous infusion through a Y-connector immediately followed by fluorouracil 400 mg/m² IV bolus then 5-fluoruracil (5-FU) 2400 mg/m² over 46 hours continuous infusion.
干预措施: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan (Drug)
B=Control group
mFOLFOX6 + Panitumumab mFOLFOX6 every 2 weeks: oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² IV infusion over 2 hours followed by fluorouracil 400 mg/m² IV bolus then 5-FU 2400 mg/m² over 46 hours continuous infusion.
干预措施: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil (Drug)
结局指标
主要结局
Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.
时间窗: 12 months after inclusion
次要结局
未报告次要终点