Combination Chemotherapy in Treating Patients With Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Time Finding Study of Chronomodulated Irinotecan, 5 Fluorouracil, Leucovorin and Oxaliplatin as First or Second Chemotherapy Line Against Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00039208
• Other study ID #: EORTC-05011
• Secondary ID: EORTC-05011
• Status: Completed
• Phase: Phase 2
• First received: June 6, 2002
• Last updated: July 12, 2012
• Start date: February 2002

Study information

• Verified date: July 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• fluorouracil

• irinotecan hydrochloride

• leucovorin calcium

• oxaliplatin

Locations

Country	Name	City	State
Belgium	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Belgium	Clinique Saint-Joseph	Liege
Belgium	Clinique Sainte Elisabeth	Namur
Belgium	Centre Hospitalier Peltzer-La Tourelle	Verviers
France	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
Italy	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
Portugal	Hospital Fernando Fonseca	Amadora

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Italy,  Portugal, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy			Yes
Secondary	Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy, excluding those who stopped prior to course 3 for reasons other than toxicity			Yes
Secondary	Peak delivery time for CPT11 activity over the first 3 courses			No
Secondary	Peak delivery time for CPT11 tolerability and efficacy over the first 6 courses			Yes
Secondary	Severe toxic events assessed by CTC v2.0 after each course of chemotherapy			Yes
Secondary	Progression-free survival			No
Secondary	Overall survival			No