Trial Comparing Two Strategies of Chemotherapy for Metastatic Colorectal Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2006 by Gustave Roussy, Cancer Campus, Grand Paris.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Fondation Francaise de Cancerologie Digestive
Sanofi
Information provided by:
Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier:
NCT00126256
First received: August 2, 2005
Last updated: September 7, 2006
Last verified: September 2006
  Purpose

The standard treatment of metastatic colorectal cancer is based on systemic chemotherapy. Several effective drugs are currently available and can be administered either sequentially or in combination. Most patients receive 2 or 3 lines of chemotherapy. The aim of this randomized trial is to evaluate the potential benefit of a bitherapy with 5-fluorouracil (5-FU) and oxaliplatin as first line chemotherapy compared with a sequential chemotherapy with 5-FU alone as first line chemotherapy followed by the combination of 5-FU with oxaliplatin in case of progressive disease, in terms of progression-free survival and overall survival in patients with advanced colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Metastasis
Drug: 5-fluorouracil
Drug: leucovorin
Drug: irinotecan
Drug: oxaliplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Trial of Treatment Strategy for Chemotherapy in Colorectal Cancer, FFCD 2000-05

Resource links provided by NLM:


Further study details as provided by Gustave Roussy, Cancer Campus, Grand Paris:

Primary Outcome Measures:
  • Progression-free survival after two lines of chemotherapy, defined as the time duration from randomization until progression after two lines of chemotherapy or death whatever the cause in the absence of progression or last-follow-up

Secondary Outcome Measures:
  • Overall survival
  • Secondary surgery
  • Response rate
  • Progression-free survival after the first and the third line of chemotherapy
  • Safety
  • Quality of life
  • Costs

Estimated Enrollment: 570
Study Start Date: February 2002
Estimated Study Completion Date: February 2006
  Hide Detailed Description

Detailed Description:

Background:

The addition of oxaliplatin and irinotecan to 5-FU improves tumor response rate and progression-free survival in patients with advanced colorectal cancer compared with 5-FU alone, but increases toxicity. It is not clear whether such combination therapies (5-FU+oxaliplatin or 5-FU+irinotecan) should be systematically used as first line treatment or as second line treatment after 5-FU failure.

Design: open-label, multicentric, randomized trial

Aim: The main objective of this multiline strategy trial was to compare two 5-FU based regimens with or without the addition of oxaliplatin to 5-FU in the first line setting in terms of progression-free survival after two lines of chemotherapy in patients with metastatic colorectal cancer.

Treatment compared:

Control arm: first line, 2-hour infusion 400 mg/m² leucovorin (LV) followed by 5-fluorouracil 400 mg/m² and 46-hours 2,400 mg/m² every 2 weeks (LV5FU2), second line, LV5FU2 + oxaliplatin 100 mg/m² as a 2-hour perfusion on day 1 (FOLFOX6), third line, LV5FU2 + irinotecan 180 mg/m² (FOLFIRI)

Experimental arm: first line, FOLFOX6, second line, FOLFIRI, third line, 5-FU 250 mg/m²/day in continuous perfusion 7 out of 8 weeks or capecitabine 2,500 mg/m² per oral 14 out of 21 days or inclusion in a phase I

Inclusion criteria:

  • Histologically confirmed metastatic colorectal adenocarcinoma
  • Unresectable metastasis
  • Bidimensionally measurable disease (WHO criteria)
  • WHO performance status of 2 or less
  • Adequate hematologic, renal function and liver functions
  • No previous chemotherapy other than previous adjuvant chemotherapy or concomitant chemoradiotherapy with 5-fluorouracil and leucovorin for the treatment of the primary tumor completed at least 6 months before inclusion
  • Signed written inform consent
  • Quality of life questionnaire (QLQ C-30) filled out

Exclusion criteria:

  • Pregnant or breast-feeding women
  • No possible regular follow-up for psychological, social or geographical reason
  • Severe cardiac, respiratory, renal or hepatic failure
  • Active coronary heart disease
  • Central nervous system metastases
  • Past history of second malignancies
  • Another investigational drug
  • Chronic inflammatory bowel disease
  • Previous chemotherapy with irinotecan or oxaliplatin based regimens

Randomization:

Randomization is performed centrally using a minimization technique, stratifying patients according to centre, previous adjuvant treatment, WHO performance status, and number of metastatic sites

Outcomes:

Progression-free survival after two lines of chemotherapy, defined as the time duration from randomization until progression after two lines of chemotherapy or death whatever the cause in the absence of progression or last-follow-up.

Overall survival, secondary surgery, response rate, progression-free survival after the first and the third line of chemotherapy, safety, quality of life and costs

Follow-up:

Tumor assessments is performed every 8 weeks, quality of live assessment every 8 weeks until progression after 2 lines of chemotherapy or for one year if no progression. After the end of the planned treatment, patients are followed up until death or the cut-off date.

Sample size and statistical analyses:

570 patients, 285 per arm will be needed to detect a difference in median of progression-free survival after two lines of chemotherapy of 3 months from 10 months in the control arm to 13 months in the experimental arm, for a type I error of 5% and a power of 80% (bilateral log rank test).

The analysis will be performed according to the intent-to treat principle. An interim analysis is planned after the inclusion of 400 patients with 3 months follow-up or the occurrence of 250 events and reviewed by an independent data monitoring committee.

Estimated duration of the trial: accrual period, 3 years, minimum follow-up, one year

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed metastatic colorectal adenocarcinoma
  • Unresectable metastasis
  • Bidimensionally measurable disease (World Health Organization [WHO] criteria)
  • WHO performance status of 2 or less
  • Adequate hematologic functions (neutrophil count, at least 1500 per cubic millimeter; and platelet count, at least 100,000 per cubic millimetre)
  • Adequate renal function (serum creatinine, less than 125 micromol per liter)
  • Adequate liver function (bilirubin, not more than 5 times the upper limit of normal)
  • No previous chemotherapy other than previous adjuvant chemotherapy or concomitant chemoradiotherapy with 5-fluorouracil and leucovorin for the treatment of the primary tumor completed at least 6 months before inclusion
  • Signed written inform consent
  • Quality of life questionnaire (QLQ C-30) filled out

Exclusion Criteria:

  • Pregnant or breast – feeding women
  • Impossibility of regular follow-up for psychological, social or geographical reason
  • Severe cardiac, respiratory, renal or hepatic failure
  • Active coronary heart disease
  • Patients with a history of a psychological illness or condition such as to interfere with the patient’s ability to understand the requirements of the study
  • Central nervous system metastases
  • Past history of second malignancies
  • Another investigational drug
  • Chronic inflammatory bowel disease
  • Previous chemotherapy with irinotecan or oxaliplatin based regimens
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00126256

Contacts
Contact: Michel Ducreux, Pr 00 33 014-211-4308 ducreux@igr.fr
Contact: Jean-Pierre F Pignon, MD, PhD 00 33 014-211-4565 jppignon@igr.fr

Locations
France
Institut Gustave-Roussy Recruiting
Villejuif, France, 94805
Contact: Michel Ducreux, Pr    00 33 014-211-4308    ducreux@igr.fr   
Contact: Jean-Pierre F Pignon, MD, PhD    00 33 014-211-4565    jppignon@igr.fr   
Principal Investigator: Michel Ducreux, Pr         
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
Fondation Francaise de Cancerologie Digestive
Sanofi
Investigators
Principal Investigator: Michel Ducreux, Pr Gustave Roussy, Cancer Campus, Grand Paris
Study Director: Jean-Pierre F Pignon, MD, PhD Gustave Roussy, Cancer Campus, Grand Paris
  More Information

No publications provided by Gustave Roussy, Cancer Campus, Grand Paris

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00126256     History of Changes
Other Study ID Numbers: FFCD 2000 – 05, CET 815
Study First Received: August 2, 2005
Last Updated: September 7, 2006
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Gustave Roussy, Cancer Campus, Grand Paris:
Colorectal cancer
metastatic
chemotherapy
randomized trial

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Fluorouracil
Oxaliplatin
Irinotecan
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on August 28, 2014