Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Single-Agent Chemotherapy Compared With Combination Chemotherapy in Treating Patients With Colorectal Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over Pharmaceutical / Industry MSKCC-95051 P-UPJOHN-MSKCC-95051, NCI-V96-0913

Objectives

I.  Compare time to tumor progression, response rate, 1-year survival, and 
quality of life in patients with previously untreated metastatic colorectal 
cancer treated with irinotecan vs. irinotecan with fluorouracil/leucovorin 
(5-FU/CF) vs. a standard regimen of 5-FU/CF.

II.  Compare the safety of these regimens and their clinical benefit (by 
measuring weight, performance status, and tumor-related signs and symptoms).

III.  Examine possible relationships between plasma concentrations of CPT-11 
(including its active metabolite, SN-38, and the SN-38 glucuronide) and major 
toxic effects and response.

Entry Criteria

Disease Characteristics:

Histologically confirmed colorectal cancer that is metastatic
  Clinical documentation required
  No brain metastasis or carcinomatous meningitis

No disease recurrence during and for 12 months following fluorouracil-based
adjuvant chemotherapy, if given

Bidimensionally measurable metastasis on x-ray, photograph, ultrasound, CT, or
MRI
  At least 1 lesion with 1 cm or greater diameter
  Lesions assessable only by radionuclide scan not considered measurable
  Bone lesions not considered measurable

Small stable asymptomatic pleural effusion or ascites allowed
  Large pleural effusions or massive ascites must be drained or sclerosed
  prior to treatment

Prior/Concurrent Therapy:

No prior therapy for metastatic disease

Prior adjuvant fluorouracil-based chemotherapy allowed

No prior pelvic irradiation

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0-2

Life expectancy:
  At least 12 weeks

Hematopoietic:
  WBC at least 3,500
  AGC at least 1,500
  Platelets at least 100,000
  Hemoglobin at least 9.0 g/dL

Hepatic:
  Bilirubin no greater than 2.0 mg/dL
  AST no greater than 3 times normal (no greater than 5 times normal if liver
     involvement)

Renal:
  Creatinine no greater than 2.0 mg/dL

Cardiovascular:
  No myocardial infarction within 6 months
  No congestive heart failure requiring therapy

Other:
  No interstitial pneumonia or fibrosis
  No known allergy to fluorouracil
  No uncontrolled infection
  No known HIV antibody
  No psychiatric or other disorder that precludes treatment or follow-up
  No second malignancy within 5 years except:
     Adequately treated nonmelanomatous skin cancer
     In situ cervical cancer
  No other concurrent disease that according to investigator precludes entry
  No pregnant or nursing women
     Negative pregnancy test required of fertile women
  Effective contraception required of fertile patients

Expected Enrollment

Approximately 760 patients (50 patients/month) will be entered on this 
multicenter study to obtain 660 evaluable patients.

Outline

This is a randomized study.  Patients are stratified by age, performance 
status, prior fluorouracil (5-FU), and time from initial diagnosis.

Patients are randomly assigned to 1 of 3 groups:  group 1 receives irinotecan 
(CPT-11) weekly for 4 weeks; group 2 receives CPT-11 and 5-FU/leucovorin (CF) 
weekly for 4 weeks; and group 3 receives 5-FU/CF for 5 consecutive days.  
Responding or stable patients in groups 1 and 2 may be re-treated every 6 
weeks, and those in group 3 may be re-treated every 28 days.

Concurrent dexamethasone is allowed for antiemesis.  Routine use of G-CSF or 
GM-CSF is not recommended.  Prochlorperazine is not permitted on CPT-11 
treatment days.

Patients are followed for survival.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Leonard Saltz, MD, Protocol chair		Ph: 212-639-2501; 800-525-2225