Phase II Trial of FOLFOXIRI Plus Panitumumab as First-Line Treatment for Kras and Braf Wild-Type Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 10
- 主要终点
- Response Rate
研究概览
简要总结
The GONO-FOLFOXIRI regimen demonstrated higher activity and efficacy compared to FOLFIRI in a phase III trial. Panitumumab with oxaliplatin- or irinotecan-based doublets is feasible and associated with improved activity in KRAS codon 12-13 wild-type patients. BRAF and other RAS rare mutations have been suggested as additional potential biomarkers for anti-EGFR agents in metastatic colo-rectal cancer. The present study aims to demonstrate the feasibility and the activity of the first-line combination of the GONO-FOLFOXIRI regimen and Panitumumab in molecularly selected metastatic colo-rectal cancer patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Histologically confirmed colorectal adenocarcinoma;
- •Availability of formalin-fixed paraffin embedded tumor block from primary or metastasis;
- •KRAS and BRAF wild-type status of primary colorectal cancer or related metastasis;
- •Unresectable and measurable metastatic disease according to RECIST criteria;
- •Male or female, aged >/= 18 years and </= 75 years;
- •ECOG PS < 2 if aged < 71 years;
- •ECOG PS = 0 if aged 71-75 years;
- •Life expectancy of more than 3 months;
- •Adequate haematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL;
- •Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN);
- •Serum creatinine ≤ 1.5 x ULN;
- •Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
- •At least 6 weeks from prior radiotherapy and 4 weeks from surgery;
- •Written informed consent to experimental treatment and pharmacogenomic analyses;
- •Magnesium ≥ lower limit of normal;
- •Calcium ≥ lower limit of normal.
排除标准
- •Prior palliative chemotherapy;
- •Prior treatment with EGFR inhibitors;
- •Symptomatic peripheral neuropathy ≥ 2 grade NCIC-CTG criteria;
- •Presence or history of CNS metastasis;
- •Active uncontrolled infections; active disseminated intravascular coagulation;
- •Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix;
- •Clinically significant cardiovascular disease, for example cerebrovascular accidents (CVA) (≤ 6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia;
- •Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception;
- •Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment;
- •History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
研究组 & 干预措施
FOLFOXIRI + Panitumumab
PANITUMUMAB 6 mg/Kg i.v. over 1 hour followed by IRINOTECAN 150 mg/sqm i.v. over 1 hour followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hours concomitantly with L-LV 200 mg/sqm over 2 hours followed by 5-FLUOROURACIL 2400 mg/sqm c.i. over 48 hours starting on day 1 repeated every 2 weeks.
干预措施: FOLFOXIRI + Panitumumab (Drug)
结局指标
主要结局
Response Rate
时间窗: Up to 3 years (objective response will be evaluated every 8 weeks)
Response rate is defined as the fraction of treated patients who achieve a response as defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria vers. 1.1.
次要结局
- Progression Free Survival(Up to 3 years)
- Safety Profile(Up to 3 years)
- Analyses of Potential Predictive Factors(Up to 3 years)
- Overall Survival(Up to 3 years)
- Secondary Radical Surgery on Metastases(Up to 3 years)