Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00005036

Collaborator

Southwest Oncology Group (Other), Eastern Cooperative Oncology Group (Other)

560

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Mucinous Adenocarcinoma of the Colon Mucinous Adenocarcinoma of the Rectum Recurrent Colon Cancer Recurrent Rectal Cancer Signet Ring Adenocarcinoma of the Colon Signet Ring Adenocarcinoma of the Rectum Stage IIIA Colon Cancer Stage IIIA Rectal Cancer Stage IIIB Colon Cancer Stage IIIB Rectal Cancer Stage IIIC Colon Cancer Stage IIIC Rectal Cancer Stage IVA Colon Cancer Stage IVA Rectal Cancer Stage IVB Colon Cancer Stage IVB Rectal Cancer	Drug: irinotecan hydrochloride Drug: oxaliplatin Drug: leucovorin calcium Drug: fluorouracil Procedure: quality-of-life assessment	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

Evaluation of time to tumor progression, time to treatment failure, toxicity of treatment, and overall response rate in patients treated with these two regimens.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

560 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 1999

Actual Primary Completion Date :

Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: irinotecan hydrochloride Given IV Other Names: Campto Camptosar CPT-11 irinotecan U-101440E Procedure: quality-of-life assessment Ancillary studies Other Names: quality of life assessment
Experimental: 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.	Drug: oxaliplatin Given IV Other Names: 1-OHP Dacotin Dacplat Eloxatin L-OHP Drug: leucovorin calcium Given IV Other Names: CF CFR LV Drug: fluorouracil Given IV Other Names: 5-fluorouracil 5-Fluracil 5-FU Procedure: quality-of-life assessment Ancillary studies Other Names: quality of life assessment

Arm

Intervention/Treatment

Experimental: 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.

Drug: irinotecan hydrochloride

Given IV

Other Names:

Campto

Camptosar

CPT-11

irinotecan

U-101440E

Procedure: quality-of-life assessment

Ancillary studies

Other Names:

quality of life assessment

Experimental: 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.

Drug: oxaliplatin

Given IV

Other Names:

1-OHP

Dacotin

Dacplat

Eloxatin

L-OHP

Drug: leucovorin calcium

Given IV

Other Names:

CFR

Drug: fluorouracil

Given IV

Other Names:

5-fluorouracil

5-Fluracil

5-FU

Procedure: quality-of-life assessment

Ancillary studies

Other Names:

quality of life assessment

Outcome Measures

Primary Outcome Measures

Overall survival [At least 6 months]
The primary analysis for this trial will be based on a one-sided Generalized Wilcoxon test.

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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