Fluorouracil, Leucovorin, and Irinotecan in Treating Patients With Recurrent or Refractory Metastatic Unresectable Colorectal Cancer

Phase II Study of 5FU/Folinic Acid and Irinotecan as Second or Third Line Treatment in Patients With Metastatic, Unresectable, Colorectal Cancer

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and irinotecan, use different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one chemotherapy drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving fluorouracil together with leucovorin and irinotecan works in treating patients with recurrent or refractory metastatic unresectable colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: FOLFIRI regimen

Detailed Description

OBJECTIVES:

Primary

• Determine the time to progression and time to death from progression in patients with recurrent or refractory metastatic unresectable colorectal cancer treated with fluorouracil, leucovorin calcium, and irinotecan.

Secondary

• Determine the objective response and stabilization rate in patients treated with this regimen.
• Determine the time to treatment failure in patients treated with this regimen.
• Determine the duration of response in patients treated with this regimen.
• Determine overall survival rate in patients treated with this regimen.
• Determine the incidence of grade 3 or 4 toxicity in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive leucovorin calcium IV over 2 hours on day 1, irinotecan IV over 1 hour on days 1 and 3, and fluorouracil IV continuously over 46 hours beginning on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 78 patients will be accrued for this study within 18 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21000
    • Hopital Drevon
  • Lille, France, 59037
    • Centre Hospital Universitaire Hop Huriez
  • Lyon, France, 69008
    • Clinique Saint Jean
  • Marseille, France, 13008
    • Hopital Saint Joseph
  • Montfermeil, France, 93370
    • Intercommunal Hospital
  • Neuilly Sur Seine, France, F-92202
    • American Hospital of Paris
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75018
    • Hôpital Bichat - Claude Bernard
  • Paris, France, 75970
    • Hopital Tenon
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Pontoise, France, 95300
    • Clinique Ste - Marie
  • Reims, France, F-51100
    • Polyclinique de Courlancy
  • Saint Brieuc, France, F-22015
    • Clinique Armoricaine de Radiologie
  • Strasbourg, France, 67010
    • Clinique de l'Orangerie
  • Suresnes, France, 92151
    • Centre Médico-Chirurgical Foch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenocarcinoma

  • Metastatic, unresectable disease

• Meets 1 of the following criteria:

  • At least 1 unidimensionally measurable metastatic lesion at least 10 mm by spiral scan OR 20 mm by conventional scan
  • Evaluable disease
  • Evidence of disease (e.g., ascites or bone metastases) by imaging techniques

• Progressive disease as defined by 1 of the following criteria:

  • Progressive disease while receiving first-line chemotherapy
  • Recurrent disease within 6 months after completing adjuvant chemotherapy
• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 to 80

Performance status

• WHO 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase < 3 times ULN

Renal

• Not specified

Cardiovascular

• No uncontrolled angina
• No myocardial infarction within the past 6 months

Gastrointestinal

• No chronic diarrhea grade 2 or greater
• No unresolved fully or partially obstructed intestine

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other underlying disease or medical condition that would preclude study participation
• No other prior malignancy except curatively treated basal cell cancer or carcinoma in situ of the cervix
• No psychological, social, familial, or geographical condition that would preclude study follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior irinotecan

Endocrine therapy

• Not specified

Radiotherapy

• At least 3 weeks since prior radiotherapy

Surgery

• At least 3 weeks since prior surgery

Other

• No other concurrent clinical trial participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time to progression
Time to death from progression

Secondary Outcome Measures

Outcome Measure
Objective response
Time to treatment failure
Duration of response
Overall survival rate
Stabilization rate
Incidence of grade 3 or 4 toxicity

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: May Mabro, MD, Hôpital FOCH

Study record dates

Study Major Dates

• Study Start: June 1, 2002

Study Registration Dates

• First Submitted: January 9, 2004
• First Submitted That Met QC Criteria: January 11, 2004
• First Posted (Estimate): January 12, 2004

Study Record Updates

• Last Update Posted (Estimate): January 6, 2009
• Last Update Submitted That Met QC Criteria: January 3, 2009
• Last Verified: August 1, 2007

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000347378; FRE-GERCOR-FOLFIRI3-C00-2; EU-20333