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
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
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.
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.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (ECOG 0-1 vs 2), primary indicator lesion (hepatic vs pulmonary vs other), age (less than 65 vs at least 65 years), alkaline phosphatase (less than 2 vs at least 2 times ULN), fluorouracil failure (adjuvant vs metastatic), and membership (intergroup vs expanded participation project). Patients are randomized to one of two treatment arms.
ARM I: Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: 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.
Patients who experience progression or toxicity on the initial regimen may crossover to the other regimen. At least 3 weeks must elapse between regimens.
Quality of life is assessed at baseline, prior to each chemotherapy course, at crossover, and at the end of the study.
Patients are followed every 6 months for 3 years or until death.
Inclusion Criteria:
Histologically or cytologically confirmed locally advanced, locally recurrent,or metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy
Progressive disease following:
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