Randomized Phase II Study for Evaluation of Efficacy and Safety of Maintenance Treatment With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction Treatment With mFOLFOX6 Plus Panitumumab and Re-induction With mFOLFOX6 Plus Panitumumab in Case of Progression for First-line Treatment of Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 387
- 试验地点
- 2
- 主要终点
- Progression-free survival
研究概览
简要总结
This is a phase II, randomized, multi-center, open-label, parallel-group study to evaluate the progression-free survival during maintenance therapy.
Eligible patients will be treated within a 12-week induction therapy. Those patients achieving CR/PR or SD at 12 weeks and qualifying for maintenance treatment and re-induction treatment with all potential drug components, will be randomized in a ratio of 1:1 to receive chemotherapy plus panitumumab or chemotherapy alone during maintenance. In case of progression, re-induction treatment will be started.
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
- •Signed written informed consent
- •Male or female ≥ 18 years of age
- •Histologically proven metastatic colorectal cancer
- •Molecular testing showing RAS wild-type in colorectal carcinoma cells
- •Life expectancy > 12 weeks
- •At least one measurable lesion according to RECIST 1.1
- •Adequate bone marrow, liver, kidney, organ and metabolic function
- •Bone marrow function:
- •leukocyte count ≥ 3.0 × 109/L
- •ANC ≥ 1.5 × 109/L
- •platelet count ≥ 100 × 109/L
- •hemoglobin ≥ 9 g/dL or 5.59 mmol/L (may be transfused or treated with erythropoietin to maintain/ exceed this level)
- •Hepatic function:
- •Total bilirubin ≤ 1.5 × UNL
- •ALT and AST ≤ 2.5 × UNL (or ≤ 5 × UNL in presence of liver metastases)
- •AP ≤ 5 × UNL
- •Renal function:
- •Creatinine clearance ≥ 50 mL/min according to Cockcroft-Gault formula or serum creatinine ≤ 1.5 × UNL
- •Metabolic function:
- •Magnesium ≥ lower limit of normal
- •Calcium ≥ lower limit of normal
- •ECOG performance status 0 - 1
- •Women of child-bearing potential must have a negative pregnancy test
排除标准
- •Previous treatment for colorectal cancer in the metastatic setting
- •Previous EGFR-targeting therapy < 6 months after end of adjuvant therapy
- •Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
- •Chronic inflammatory bowel disease
- •Peripheral neuropathy ≥ NCI-CTCAE V 4.03 grade 2
- •Other previous malignancies with the exception of a history of previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix or other curatively treated malignant disease without recurrence after at least 5 years of follow-up
- •Significant disease that, in the investigator's opinion, would exclude the patient from the study
- •History of cardiac disease; defined as:
- •Congestive heart failure > New York Heart Association (NYHA) class 2
- •Active coronary artery disease (myocardial infarction more than 6 months prior to start of study treatment is allowed)
- •Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
- •Uncontrolled hypertension (defined as blood pressure ≥ 160 mmHg systolic and/or ≥ 90 mmHg diastolic on medication)
- •Patients with interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
- •Known HIV, hepatitis B or C infection
- •Known hypersensitivity reaction to any of the study components
- •Radiotherapy, major surgery or any investigational drug 30 days before registration
- •Pregnancy or lactation or planning to be pregnant during treatment and within 6 months after the end of treatment
- •Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for at least an additional 6 months after the end of treatment
- •Known alcohol or drug abuse
- •Any condition that is unstable or could jeopardize the safety of the patient and his compliance in the study
研究组 & 干预措施
Maintenance Chemotherapy + Panitumumab
Maintenance therapy:
Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Re-induction upon progression:
Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy.
mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
干预措施: Maintenance Chemotherapy (Drug)
Maintenance Chemotherapy + Panitumumab
Maintenance therapy:
Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Re-induction upon progression:
Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy.
mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
干预措施: Panitumumab (Within maintenance phase) (Drug)
Maintenance Chemotherapy + Panitumumab
Maintenance therapy:
Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Re-induction upon progression:
Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy.
mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
干预措施: mFOLFOX6 (Within re-induction phase) (Drug)
Maintenance Chemotherapy + Panitumumab
Maintenance therapy:
Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Re-induction upon progression:
Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy.
mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
干预措施: Panitumumab (Within re-induction phase) (Drug)
Maintenance Chemotherapy w/o Panitumumab
Maintenance therapy:
Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Re-induction upon progression:
Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy.
mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
干预措施: Maintenance Chemotherapy (Drug)
Maintenance Chemotherapy w/o Panitumumab
Maintenance therapy:
Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Re-induction upon progression:
Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy.
mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
干预措施: mFOLFOX6 (Within re-induction phase) (Drug)
Maintenance Chemotherapy w/o Panitumumab
Maintenance therapy:
Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Re-induction upon progression:
Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy.
mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
干预措施: Panitumumab (Within re-induction phase) (Drug)
结局指标
主要结局
Progression-free survival
时间窗: Until end of follow-up (24 months after randomization)
Progression-free survival during maintenance therapy defined as time from randomization until disease progression or death, whatever occurs first.
次要结局
- failure of treatment strategy(Until end of follow up (24 months after randomization))
- Progression-free survival of re-induction(From start of re-induction therapy until progress or end of follow-up (24 months after randomization))
- Objective response after 12 weeks of induction chemotherapy(12 weeks after start of induction chemotherapy)
- Objective best response during maintenance and re-induction(Start of maintenance- until end of re-inductin therapy (expected average of 8 months))
- Overall survival(Until end of follow-up (24 months after randomization))
- Safety(Until end of follow-up (24 months after randomization))
- Health and skin related Quality of life(Until end of follow-up (24 months after randomization))