Combination Chemotherapy in Treating Patients With Colorectal Cancer

NCT ID: NCT00039208

Last Updated: 2012-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28

Brief Summary

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.

Detailed Description

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.

Conditions

Colorectal Cancer

Keywords

stage III colon cancer; stage IV colon cancer; stage III rectal cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

fluorouracil

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carlo Garufi, MD

Role: STUDY_CHAIR

Istituti Fisioterapici Ospitalieri - Roma

Locations

Centre Hospitalier Notre Dame - Reine Fabiola

Charleroi, , Belgium

Clinique Saint-Joseph

Liège, , Belgium

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, , Belgium

Clinique Sainte Elisabeth

Namur, , Belgium

Centre Hospitalier Peltzer-La Tourelle

Verviers, , Belgium

Centre Jean Perrin

Clermont-Ferrand, , France

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Centre Hospital Regional Universitaire de Limoges

Limoges, , France

Hopital Saint-Louis

Paris, , France

Centre Rene Huguenin

Saint-Cloud, , France

Hopital Paul Brousse

Villejuif, , France

Azienda Sanitaria di Bolzano

Bolzano, , Italy

Universita G.D'Annunzio Di Chieti

Chieti, , Italy

Ospedale San Carlo Borromeo

Milano (Milan), , Italy

Azienda Ospedale S. Luigi at University of Torino

Orbassano, (Torino), , Italy

Fondazione Salvatore Maugeri

Pavia, , Italy

Ospedale Oncologico Regionale

Rionero in Vulture, , Italy

Istituto Regina Elena

Rome, , Italy

Istituto Clinico Beato Matteo

Vigevano, , Italy

Hospital Fernando Fonseca

Amadora, , Portugal

Countries

Belgium; France; Italy; Portugal

References

Garufi C, Focan C, Tumolo S, et al.: Time finding study of chronomodulated irinotecan (I), fluorouracil (F), leucovorin (L) and oxaliplatin (O) (chronoIFLO) against metastatic colorectal cancer: results from randomized EORTC 05011 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-2566, 2007.

Reference Type: RESULT

Other Identifiers

EORTC-05011

Identifier Type: -

Identifier Source: secondary_id

EORTC-05011

Identifier Type: -

Identifier Source: org_study_id