Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

January 29, 2010 updated by: GERCOR - Multidisciplinary Oncology Cooperative Group

Phase II-III Study of an Optimized LV-5FU-Oxaliplatin Strategy in Metastatic Colorectal Cancer. Optimox2 Study. C02-2

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating colorectal cancer.

PURPOSE: This randomized phase II/III trial is studying two combination chemotherapy regimens to compare how well they work in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare progression-free survival of patients with inoperable metastatic colorectal cancer treated with oxaliplatin, leucovorin calcium, and fluorouracil with vs without maintenance leucovorin calcium and fluorouracil.
  • Demonstrate that time of disease control (TDC) can be increased by 15% at 9 months and that maintenance therapy can be avoided.

Secondary

  • Compare the overall survival and response rate in patients treated with these regimens.
  • Compare the salvage surgery rate in patients treated with these regimens.
  • Compare the tolerability of these regimens in these patients.
  • Compare the quality of life in patients treated with these regimens.
  • Compare the duration of chemotherapy-free intervals in patients treated with these regimens.
  • Compare the pharmacoeconomy and pharmacogenetics of these regimens in these patients.

OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are stratified according to participating center, performance status (0-1 vs 2), number of metastatic sites (1 vs > 1), age (18-50 years vs 51-75 years vs 76-80 years), adjuvant chemotherapy, and baseline alkaline phosphatase (≤ 3 times upper limit of normal [ULN] vs > 3 times ULN). Patients are randomized to 1 of 2 treatment arms.

Arm I

  • FOLFOX chemotherapy: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance chemotherapy.
  • Maintenance chemotherapy: Patients receive leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Patients with disease progression on maintenance chemotherapy receive 6 additional courses of FOLFOX as above. Patients with continued disease progression while receiving the additional courses of FOLFOX proceed to irinotecan-based chemotherapy off study.

Arm II

  • FOLFOX chemotherapy: Patients receive 6 courses of FOLFOX as in arm I. Patients with disease progression on FOLFOX receive 6 additional courses of FOLFOX. Patients with continued disease progression while receiving the additional courses of FOLFOX proceed to irinotecan-based chemotherapy off study.

In both arms, patients with stable or responding disease may undergo surgical resection after completion of the initial 6 courses of FOLFOX.

Quality of life is assessed at baseline, after courses 4 and 6, and then every 2-3 months thereafter.

After completion of study treatment, patients are followed at 1 month and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

600

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Avignon, France, 84902
        • Hopital Duffaut
      • Avignon, France, 84082
        • Institut Sainte Catherine
      • Caluire, France, 69300
        • Infirmerie Protestante
      • Dijon, France, 21000
        • Hopital Drevon
      • Dreux, France, 28100
        • Centre Hospitalier de Dreux
      • Le Coudray, France, 28630
        • Hopital Louis Pasteur - Le Coudray
      • Le Mans, France, F-72000
        • Clinique Victor Hugo
      • Libourne, France, 33500
        • Hôpital Robert Boulin
      • Lyon, France, 69008
        • Clinique Saint Jean
      • Montfermeil, France, 93370
        • Intercommunal Hospital
      • Paris, France, 75015
        • Hôpital Europeén Georges Pompidou
      • Paris, France, 75970
        • Hôpital Tenon
      • Paris, France, 75571
        • Hopital Saint Antoine
      • Reims, France, F-51100
        • Polyclinique de Courlancy
      • Senlis, France, 60309
        • C.H. Senlis
      • Senlis, France, 60309
        • Clinique des Jockeys
      • Suresnes, France, 92151
        • Centre Medico-Chirurgical Foch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 proven adenocarcinoma of the colon or rectum

    • Metastatic disease

      • No metastases involving only the bone
  • Inoperable disease (i.e., not suitable for complete surgical resection)

  • Measurable or evaluable disease

    • Measurable disease defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional CT scan OR ≥ 10 mm by spiral CT scan
  • No symptomatic ascites or pleural effusion that has not been evacuated
  • No CNS metastasis

PATIENT CHARACTERISTICS:

  • WHO OR ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelets ≥ 100,000/mm^3
  • Creatinine < 3 times upper limit of normal (ULN)
  • Alkaline phosphatase < 5 times ULN
  • No peripheral neuropathy ≥ grade 1
  • No total or partial bowel obstruction
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No uncontrolled hypercalcemia
  • No other concurrent or prior malignancy, except adequately treated carcinoma in situ of the uterine cervix or basal or squamous cell carcinoma of the skin or cancer in complete remission for ≥ 5 years
  • No uncontrolled congestive heart failure
  • No angina pectoris
  • No hypertension
  • No arrhythmias
  • No history of significant neurologic or psychiatric disorders
  • No active infection
  • No other serious nonmalignant disease

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy and/or immunotherapy for metastatic disease
  • Prior adjuvant chemotherapy allowed provided progression-free interval after completion of adjuvant chemotherapy is > 6 months
  • No other concurrent anticancer treatment
  • No participation in another clinical trial with any investigational drug within 30 days prior to randomization
  • No other concurrent investigational treatment
  • No concurrent radiotherapy
  • No concurrent cold cap for prevention of alopecia or iced mouth rinses for prevention of stomatitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Overall survival
Time to disease control
Response as measured by RECIST criteria
Quality of life as assessed by EUROQOL- 5 Dimensional Instrument or Functional Assessment of Cancer Therapy-Neurotoxicity module version 4.0 at baseline and periodically during study treatment
Pharmaco-economic evaluation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GERCOR - Multidisciplinary Oncology Cooperative Group

Investigators

  • Study Chair: Aimery de Gramont, MD, Hopital Saint Antoine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2004

Study Registration Dates

First Submitted

January 10, 2006

First Submitted That Met QC Criteria

January 10, 2006

First Posted (Estimate)

January 11, 2006

Study Record Updates

Last Update Posted (Estimate)

February 1, 2010

Last Update Submitted That Met QC Criteria

January 29, 2010

Last Verified

May 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000453890
  • GERCOR-OPTIMOX2
  • GERCOR-OPTIMOX2-2003
  • GERCOR-OPTIMOX2-C02-2
  • EU-20566
  • SANOFI-GERCOR-OPTIMOX2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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