RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs at the time of day that allows for the best drug response may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Randomized phase II trial to determine the best time to give irinotecan combined with fluorouracil, leucovorin, and oxaliplatin in treating patients who have colorectal cancer.

Condition	Treatment or Intervention	Phase
stage III colon cancer stage IV colon cancer stage III rectal cancer Stage IV rectal cancer recurrent colon cancer recurrent rectal cancer	Drug: fluorouracil  Drug: irinotecan  Drug: leucovorin calcium  Drug: oxaliplatin  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the role of peak delivery time on the tolerability of irinotecan when administered with chronomodulated fluorouracil, leucovorin calcium, and oxaliplatin as first- or second-line therapy in patients with locoregional or metastatic colorectal cancer.
• Determine the antitumor activity of this regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, WHO performance status (0-1 vs 2), and line of treatment (first vs second). Patients are randomized to receive irinotecan at 1 of 6 different times of the day.

Patients receive irinotecan IV over 6 hours on day 1 and fluorouracil IV and leucovorin calcium IV over 11 hours followed by oxaliplatin IV over 11 hours on days 2-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 4 weeks until disease progression and then every 8 weeks thereafter.

PROJECTED ACCRUAL: A maximum of 186 patients (31 per irinotecan administration time) will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer
• Unresectable metastatic or locoregional disease
• At least 1 measurable lesion outside a previously irradiated area or an area treated with physical devices (e.g., cryotherapy, laser, or thermoablation)
• No prior enrollment in EORTC-05963
• No symptomatic brain metastases

PATIENT CHARACTERISTICS: Age:

• Over 18

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count greater than 2,000/mm^3
• Platelet count at least 90,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)

Renal:

• Creatinine no greater than 1.5 times ULN
• No uncontrolled hypercalcemia

Cardiovascular:

• No overt cardiac disease

Pulmonary:

• No severe respiratory illness

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Male patients must use effective barrier contraception during and for up to 6 months after study
• No baseline diarrhea greater than grade I (must have less than 4 stools per 24 hours)
• No prior grade III or IV toxicity related to irinotecan
• No sensory or motor neuropathy with functional impairment
• No prior hypersensitivity to any study drug
• No other primary tumor except basal cell skin cancer or carcinoma in situ of the cervix
• No uncontrolled infectious or chronic disease
• No psychological, familial, sociological, or geographical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent prophylactic growth factor therapy

Chemotherapy:

• At least 1 month since prior chemotherapy
• No prior irinotecan, fluorouracil, leucovorin calcium, and oxaliplatin as combination therapy
• Other prior therapy containing irinotecan and/or oxaliplatin allowed
• No more than 1 prior chemotherapy regimen for metastatic or locoregional disease
• Adjuvant chemotherapy considered first-line therapy if tumor relapsed within 6 months of completion of therapy

Endocrine therapy:

• No concurrent corticosteroids except for emergencies

Radiotherapy:

• See Disease Characteristics
• Palliative radiotherapy for bone lesion allowed except for disease progression

Surgery:

• See Disease Characteristics

Belgium
      Centre Hospitalier Notre Dame - Reine Fabiola, Charleroi,  6000,  Belgium; Recruiting
      Centre Hospitalier Peltzer-La Tourelle, VERVIERS,  B-4800,  Belgium; Recruiting
      CHU Liege - Domaine Universitaire du Sart Tilman, LIEGE,  B-4000,  Belgium; Recruiting
      Clinique Sainte Elisabeth, Namur,  5000,  Belgium; Recruiting
      Clinique Saint-Joseph, LIEGE,  B 4000,  Belgium; Recruiting
France
      Centre de Lutte Contre le Cancer Georges-Francois Leclerc, Dijon,  21079,  France; Recruiting
      Centre Hospital Regional Universitaire de Limoges, Limoges,  87042,  France; Recruiting
      Centre Jean Perrin, Clermont-Ferrand,  63011,  France; Recruiting
      Centre Rene Huguenin, Saint Cloud,  92211,  France; Recruiting
      Hopital Paul Brousse, Villejuif,  94804,  France; Recruiting
      Hopital Saint-Louis, Paris,  75475,  France; Recruiting
Italy
      Azienda Ospedale S. Luigi - Universita Di Turin, Orbassano, (Torino),  10043,  Italy; Recruiting
      Azienda Sanitaria di Bolzano, Bolzano,  39100,  Italy; Recruiting
      Fondazione Salvatore Maugeri, Pavia,  I-27100,  Italy; Recruiting
      Istituto Clinico Beato Matteo, Vigevano,  27029,  Italy; Recruiting
      Istituto Regina Elena, Rome,  00161,  Italy; Recruiting
      Ospedale Oncologico Regionale, Rionero in Vulture,  I-58028,  Italy; Recruiting
      Ospedale San Carlo Borromeo, Milano (Milan),  20153,  Italy; Recruiting
      Universita G.D'Annunzio Di Chieti, Chieti,  66100,  Italy; Recruiting
Portugal
      Hospital Fernando Fonseca, Amadora,  P-2700,  Portugal; Recruiting

Study chairs or principal investigators

Carlo Garufi, MD,  Istituti Fisioterapici Ospitalieri - Roma   

Study ID Numbers:  CDR0000069363; EORTC-05011; NCT00039208
Record last reviewed:  January 2005
Last Updated:  March 3, 2005
Record first received:  June 6, 2002
ClinicalTrials.gov Identifier:  NCT00039208
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08