Intermittent or Continuous Panitumumab Plus FOLFIRI for First-line Treatment of Patients With RAS/B-RAF Wild-type Metastatic Colorectal Cancer: a Randomized Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 151
- 试验地点
- 1
- 主要终点
- Progression-free Survival
研究概览
简要总结
The investigators hypothesize that intermittent first-line Panitumumab plus FOLFIRI is effective as the same regimen given continuously, in unresectable metastatic RAS and BRAF wild type colorectal cancer patients. Correlative studies on tumor and blood samples could identify potential biomarkers of efficacy and help defining personalized treatment strategy.
详细描述
This will be a multicenter open label randomized phase II study. The study population will include untreated RAS wild-type metastatic colorectal (mCRC) patients with unresectable disease. A total of 136 patients will be enrolled.
All Patients will receive an induction treatment with panitumumab as 1 hour intravenous infusion at the dosage of 6 mg/kg, given every two weeks, plus FOLFIRI chemotherapy as standard guidelines.
Before start of FOLFIRI plus panitumumab, at the time of enrollment, patients will be immediately randomized electronically 1:1 to one of the two arms. Induction treatment with FOLFIRI plus panitumumab will continue until progressive disease, unacceptable toxicity or informed consent withdrawal, or for up to 8 cycles. At the end of induction treatment, in presence of complete or partial response, or stable disease, non-progressing patients will be allocated to one of the two pre-assigned arms:
A) CONTINOUS: FOLFIRI plus panitumumab until progressive disease, unacceptable toxicity or informed consent withdrawal. Panitumumab will be administered as a 6 mg/kg intravenous infusion over 60 minutes (day 1) every 2 weeks. The dose of Panitumumab should be administered prior to chemotherapy. Irinotecan will be administered as a 180 mg/m2 intravenous infusion over 60 minutes (day 1) every 2 weeks. Folinic acid will be administered as a 200 mg/m2 intravenous infusion over 120 minutes before 5- fluorouracil infusion (day 1) every 2 weeks. 5-fluorouracil will be administered as a 400 mg/m2 intravenous bolus injection (day 1) followed by 2400 mg/m246-hours continuous infusion (day 1), every 2 weeks. Cycle length will be 2 weeks +/- 3 days.
B) INTERMITTENT: treatment free interval until progressive disease; followed by up to 8 cycles of FOLFIRI plus panitumumab; in presence of complete or partial response, or stable disease, non-progressing patients will undergo again to treatment free interval until PD, when they will restart treatment. Treatment cycling will continue till any progressive disease on treatment. Panitumumab will be administered at same dose and infusion with FOLFIRI.
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
- •Written informed consent to study procedures and to molecular analyses;
- •Histologically proven diagnosis of colorectal cancer with wildtype RAS and BRAF status in certified laboratories;
- •Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
- •At least one measurable lesion according to RECIST1.1 criteria;
- •Availability of a tumor sample (primary and/or metastatic sites) for exploratory research;
- •Age ≥ 18 years;
- •ECOG PS ≤ 2;
- •Life expectancy of at least 12 weeks;
- •Previous adjuvant chemotherapy allowed only if more than 6 months elapsed between the end of adjuvant and first relapse;
- •Neutrophils ≥ 1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl;
- •Total bilirubin ≤1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or < 5 x UNL in case of liver metastases) alkaline phosphatase ≤ 2.5 x UNL (or < 5 x UNL in case of liver metastases);
- •Creatinine clearance ≥50 mL/min or serum creatinine ≤ 1.5 x UNL;
- •Female with a childbearing potential and male subjects must be willing to use adequate contraception (barrier contraceptive measure, oral contraception, intrauterine device);
- •Will and ability to comply with the protocol.
排除标准
- •Previous treatment for metastatic disease;
- •Radiotherapy to any site within 4 weeks before the study;
- •Any contraindication to use Panitumumab, Irinotecan, 5-FU or folinic acid
- •Known or clinically suspected brain metastases.
- •History or evidence upon physical examination of CNS disease unless adequately treated.
- •Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks.
- •Diagnosis of interstitial pneumonitis or pulmonary fibrosis;
- •Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration or which, in the investigating physician's opinion, rules out the patient's participation in the study;
- •Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication;
- •Treatment with any investigational drug within 30 days prior to enrolment;
- •Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ;
- •Lack of physical integrity of the gastrointestinal tract or history of acute or sub-acute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea.
- •Disease that is deemed potentially resectable.
- •Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
- •Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.
- •Breastfeeding
- •Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
研究组 & 干预措施
CONTINUOUS ARM:
Patients will receive Panitumumab plus FOLFIRI until progressive disease, unacceptable toxicity or informed consent withdrawal.
干预措施: Panitumumab (Drug)
INTERMITTENT ARM:
Patients will have a treatment free interval until progressive disease (PD), when they will receive up to 8 cycles of Panitumumab plus FOLFIRI. In the presence of complete or partial response, or stable disease, non-progressing patients will undergo again to treatment free interval until PD, when they will restart treatment. Treatment cycling will continue till any PD on treatment.
干预措施: Panitumumab (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: up to 1 year last patients randomized
Progression Free Survival on treatment (PFSOT) is defined as the time from randomization to the first objective disease progression documented in patients undergoing treatment cycle (objective disease progression during treatment free intervals are excluded) or death due to any cause, whichever occurs first.
次要结局
- Overall Survival (OS)(up to 1 year last patients randomized)