First Line Infusional 5-Fluorouracil, Folinic Acid and Oxaliplatin for Metastatic Colorectal Cancer or Loco-Regional Recurrency - Role of Chronomodulated Delivery Upon Survival - A Multicenter Randomized Phase III Trial
18 Years
75 Years
Both
Colorectal Cancer
Trial Information
First Line Infusional 5-Fluorouracil, Folinic Acid and Oxaliplatin for Metastatic Colorectal Cancer or Loco-Regional Recurrency - Role of Chronomodulated Delivery Upon Survival - A Multicenter Randomized Phase III Trial
OBJECTIVES: I. Compare the effects of chronomodulated versus nonchronomodulated infusional
administration of a 3 drug high-dose chemotherapy regimen on survival in patients with
locoregionally recurrent or metastatic colorectal cancer. II. Assess the antitumor effect of
the combination of fluorouracil, leucovorin calcium, and oxaliplatin given as first line
chemotherapy in these patients. III. Assess the response rate and toxicity of this treatment
in these patients. IV. Assess the quality of life of patients receiving this treatment.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
performance status (ECOG 0-1 vs 2), extent of liver involvement (none vs less than 25% vs
25% or greater), and institution. Patients are randomized into 2 arms: Arm I
(chronotherapy): Patients receive a 4 day infusion of fluorouracil, leucovorin calcium, and
oxaliplatin administered via pump using chronomodulated delivery rates. Arm II (fixed
infusion rate): Patients receive leucovorin calcium and oxaliplatin as 2 hour concurrent
infusions followed by fluorouracil as a 22 hour infusion on day 1. On day 2, patients
receive a 2 hour infusion of leucovorin calcium followed by a 22 hour infusion of
fluorouracil. For patients on both arms, courses repeat every 2 weeks until the occurrence
of disease progression, severe toxicity, or complete remission for a minimum of 4 months.
Quality of life is assessed prior to treatment and 2 weeks after courses 4 and 8. Patients
are followed for survival.
PROJECTED ACCRUAL: A total of 554 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically proven locoregionally recurrent or metastatic
adenocarcinoma of the colon or rectum Histologic or cytologic proof of adenocarcinoma
consistent with colorectal cancer in a solitary lesion if plasma carcinoembryonic antigen
level is no greater than normal Metastases not limited to bone, pleural effusion, or
ascites Surgically resectable metastases not eligible No symptomatic brain metastasis At
least one bidimensionally measurable lesion measuring at least 20 mm in one diameter
outside a previously irradiated area
PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: ECOG 0-2 Life expectancy: Not
specified Hematopoietic: Absolute neutrophil count at least 2,000/mm3 Platelet count at
least 100,000/mm3 Hepatic: Bilirubin no greater than 3 times upper limit of normal Renal:
No uncontrolled hypercalcemia Cardiovascular: No significant cardiac disease Pulmonary: No
severe respiratory illness Neurologic: No peripheral sensory neuropathy Other: No
uncontrolled infection or chronic disease No second malignancy except basal cell carcinoma
of the skin or in situ carcinoma of the cervix
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy for locoregionally
recurrent or metastatic colorectal cancer No concurrent prophylactic growth factor
Chemotherapy: No prior chemotherapy for locoregionally recurrent or metastatic colorectal
cancer At least 6 months since adjuvant chemotherapy Endocrine therapy: No prior hormone
therapy for locoregionally recurrent or metastatic colorectal cancer No concurrent
corticosteroids Radiotherapy: See Disease Characteristics No prior radiotherapy for
locoregionally recurrent or metastatic colorectal cancer Concurrent localized analgesic
radiotherapy of a bone lesion permitted unless indicative of disease progression Surgery:
No prior surgery for locoregionally recurrent or metastatic colorectal cancer Other: No
other concurrent investigational drug
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Principal Investigator
Francis Levi, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Institut de Cancerologie et D'Immunogenetique at Hopital Paul-Brousse
Authority:
United States: Federal Government
Study ID:
EORTC-05963
NCT ID:
NCT00003287
Start Date:
March 1998
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage IV colon cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- adenocarcinoma of the colon
- adenocarcinoma of the rectum
- Colorectal Neoplasms
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