A Randomized Phase III Equivalence Trial of Irinotecan (CPT-11) Versus Oxaliplatin (OXAL)/5-Fluorouracil (5-FU)/Leucovorin (CF) in Patients With Advanced Colorectal Carcinoma Previously Treated With 5-FU
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 560
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
Randomized phase III trial to compare the effectiveness of irinotecan with that of combination chemotherapy in treating patients who have advanced colorectal cancer that has not responded to previous treatment. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for colorectal cancer.
详细描述
PRIMARY OBJECTIVES:
I. Determine whether in advanced colorectal carcinoma patients who have been previously treated with 5-FU, the overall survival of patients treated with OXAL + 5-FU + CF followed by CPT-11 is equivalent to the survival of patients treated with CPT-11 followed by OXAL + 5-FU + CF.
SECONDARY OBJECTIVES:
I. Evaluation of time to tumor progression, time to treatment failure, toxicity of treatment, and overall response rate in patients treated with these two regimens.
II. To compare quality-of-life measurements patients treated with these two regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Histologically or cytologically confirmed locally advanced, locally recurrent,or metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy
- •Progressive disease following:
- •One prior fluorouracil based chemotherapy regimen for metastatic disease
- •Failure during or within 6 months after fluorouracil based adjuvant therapy
- •Measurable or evaluable disease
- •No CNS metastases or carcinomatous meningitis
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 9 g/dL (transfusion allowed)
- •Bilirubin no greater than 1.5 mg/dL
- •AST no greater than 5 times upper limit of normal (ULN)
- •Alkaline phosphatase no greater than 5 times ULN
- •Creatinine no greater than 1.5 times ULN
- •No uncontrolled high blood pressure
- •No unstable angina
- •No symptomatic congestive heart failure
- •No myocardial infarction with the past 6 months
- •No serious uncontrolled cardiac arrhythmias
- •No New York Heart Association class III or IV heart disease
- •No pleural effusion or ascites that cause respiratory compromise (e.g., dyspnea grade 2 or greater)
- •No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •Fluent in English
- •No active or uncontrolled infection
- •No other prior malignancy within the past 5 years, except:
- •Adequately treated basal or squamous cell skin cancer
- •Adequately treated noninvasive carcinomas
- •No sensory neuropathy grade 2 or greater
- •No uncontrolled colonic or small bowel disorders (greater than 3 loose stools daily)
- •No concurrent sargramostim (GM-CSF)
- •At least 4 weeks since prior chemotherapy and recovered
- •No more than 1 prior chemotherapy regimen for advanced colorectal cancer
- •No prior irinotecan or other camptothecin derivative (e.g., topotecan)
- •No prior oxaliplatin
- •No other concurrent investigational chemotherapy agents
- •At least 4 weeks since prior major radiotherapy
- •No prior radiotherapy to greater than 25% of bone marrow
- •At least 4 weeks since prior major surgery and recovered
- •At least 2 weeks since prior minor surgery and recovered
排除标准
- 未提供
研究组 & 干预措施
Arm II (oxalipatin, fluorouracil, leucovorin calcium)
Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: oxaliplatin (Drug)
Arm I (irinotecan)
Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: irinotecan hydrochloride (Drug)
Arm I (irinotecan)
Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: quality-of-life assessment (Procedure)
Arm II (oxalipatin, fluorouracil, leucovorin calcium)
Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: leucovorin calcium (Drug)
Arm II (oxalipatin, fluorouracil, leucovorin calcium)
Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: fluorouracil (Drug)
Arm II (oxalipatin, fluorouracil, leucovorin calcium)
Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: quality-of-life assessment (Procedure)
结局指标
主要结局
Overall survival
时间窗: At least 6 months
The primary analysis for this trial will be based on a one-sided Generalized Wilcoxon test.
次要结局
- Time-to-tumor progression(Time from start of therapy to documentation of disease progression, assessed up to 3 years)
- Time-to-treatment failure(Time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, refusal, or death, assessed up to 3 years)
- Objective tumor response rate (CR or PR) in patients with measureable disease(At least 4 weeks)
- Toxicity and dose intensity(Up to 3 years)
- Quality of life(Up to 3 years)