Clinical trial NCT00005036: Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: SWOG Cancer Research Network
name: Eastern Cooperative Oncology Group
First posted: 2003-01-27
Enrollment: 560
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: At least 6 months
Secondary outcomes:
measure: Time-to-tumor progression
timeFrame: Time from start of therapy to documentation of disease progression, assessed up to 3 years
measure: Time-to-treatment failure
timeFrame: 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
measure: Objective tumor response rate (CR or PR) in patients with measureable disease
timeFrame: At least 4 weeks
measure: Toxicity and dose intensity
timeFrame: Up to 3 years
measure: Quality of life
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: North Central Cancer Treatment Group
state: Minnesota
Study officials:
affiliation: North Central Cancer Treatment Group
name: Henry Pitot
role: PRINCIPAL_INVESTIGATOR
References: