Comparison of Combination Chemotherapy Regimens in Treating Patients With Metastatic Colorectal Cancer

Randomized Phase II Study Evaluating Three Chemotherapies: [Irinotecan + Oxaliplatin (Irinox)], [Irinotecan + LV5FU2] and [Oxaliplatin + LV5FU2] as First Intention Treatment in Subjects With Metastatic Colorectal Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying combination chemotherapy containing irinotecan and oxaliplatin to see how well it works compared to two standard combination chemotherapy regimens in treating patients with unresectable metastatic colorectal cancer.

Study Overview

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

Detailed Description

OBJECTIVES:

• Compare the efficacy, in terms of response rate (partial response and complete response), of irinotecan and oxaliplatin vs irinotecan, fluorouracil, and leucovorin calcium vs oxaliplatin, fluorouracil, and leucovorin calcium in patients with metastatic colorectal cancer.
• Compare the progression-free survival of patients treated with these regimens.
• Compare the tolerability of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive irinotecan IV over 90 minutes and oxaliplatin IV over 2 hours on day 1.
• Arm II: Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2.
• Arm III: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2.

In all arms, treatment repeats every 2 weeks for 26 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months for 1 year.

Patients are followed at 2 months.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 1 year.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amilly, France, 45207
    • Centre Hospitalier de L' Agglomeration Montargoise
  • Angers, France, 49036
    • Pole Sante Sarthe et Loir Hopital Pierre Daguet
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Hyeres, France, 83400
    • Clinique Sainte-Marguerite
  • La Roche Sur Yon, France, F-85025
    • Centre Hospitalier departemental
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Orleans, France, 45100
    • CHR D'Orleans - Hopital de la Source
  • Perigueux, France, 24004
    • Polyclinique Francheville
  • Rennes, France, 35062
    • Centre Eugene Marquis
  • Roanne, France, F-42300
    • CHG Roanne
  • Rodez, France, 12027
    • Centre Hospitalier de Rodez
  • Saint Cloud, France, 92210
    • Centre René Huguenin
  • Thionville, France, 57126
    • Centre Hospitalier Regional Metz Thionville
  • Vienne, France, 38200
    • Centre Hospitalier General Lucien Hussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal carcinoma

  • Metastatic disease
• Not amenable to surgery
• Unidimensionally measurable disease
• No bone metastases
• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• WHO 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin no greater than 1.25 times upper limit of normal (ULN) (1.5 times ULN if hepatic metastases are present)
• SGPT and SGOT no greater than 3 times ULN (5 times ULN if hepatic metastases are present)

Renal

• Creatinine no greater than 1.25 times ULN

Cardiac

• No concurrent cardiac abnormalities that would preclude study therapy

Pulmonary

• No concurrent pulmonary abnormalities that would preclude study therapy

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No chronic enteropathy
• No other prior cancer within the past 5 years except carcinoma in situ of the cervix or curatively treated basal cell skin cancer
• No concurrent severe uncontrolled infection
• No obstruction or partial obstruction that would interfere with study therapy
• No psychological, social, familial, or geographical situation that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent anticancer biological response modifiers

Chemotherapy

• No prior chemotherapy (except adjuvant chemotherapy completed more than 6 months ago)
• No prior irinotecan
• No prior oxaliplatin
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent anticancer hormonal therapy

Radiotherapy

• At least 4 weeks since prior pelvic radiotherapy
• No prior abdominopelvic radiotherapy

Surgery

• At least 4 weeks since prior surgery
• No prior extensive intestinal resection (i.e., more than 1 prior hemicolectomy or extensive resection of the small intestines)

Other

• No other concurrent experimental medication
• No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED

Collaborators and Investigators

• Sponsor: UNICANCER

Publications and helpful links

General Publications

• Becouarn Y, Senesse P, Thezenas S, Boucher E, Adenis A, Cany L, Jacob JH, Cvitkovic F, Montoto-Grillot C, Ychou M; Digestive Group of the Federation Nationale des Centres de Lutte Contre le Cancer. A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Federation Nationale des Centres de Lutte Contre le Cancer. Ann Oncol. 2007 Dec;18(12):2000-5. doi: 10.1093/annonc/mdm379. Epub 2007 Sep 4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 23, 2002
• Primary Completion (ACTUAL): November 4, 2005
• Study Completion (ACTUAL): April 1, 2007

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (ESTIMATE): August 7, 2003

Study Record Updates

• Last Update Posted (ACTUAL): March 2, 2021
• Last Update Submitted That Met QC Criteria: February 25, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon 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; Oxaliplatin; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: Accord 08; FRE-FNCLCC-ACCORD-08/0103; EU-20233

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No