Combination Chemotherapy in Treating Patients With Colorectal Cancer

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00039208

Collaborator

(none)

Locations

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: oxaliplatin	Phase 2

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2002

Actual Primary Completion Date :

Aug 1, 2005

Outcome Measures

Primary Outcome Measures

Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy []

Secondary Outcome Measures

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 []
Peak delivery time for CPT11 activity over the first 3 courses []
Peak delivery time for CPT11 tolerability and efficacy over the first 6 courses []
Severe toxic events assessed by CTC v2.0 after each course of chemotherapy []
Progression-free survival []
Overall survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi	Belgium	6000
2	Clinique Saint-Joseph	Liege	Belgium	B 4000
3	CHU Liege - Domaine Universitaire du Sart Tilman	Liege	Belgium	B-4000
4	Clinique Sainte Elisabeth	Namur	Belgium	5000
5	Centre Hospitalier Peltzer-La Tourelle	Verviers	Belgium	B-4800
6	Centre Jean Perrin	Clermont-Ferrand	France	63011
7	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon	France	21079
8	Centre Hospital Regional Universitaire de Limoges	Limoges	France	87042
9	Hopital Saint-Louis	Paris	France	75475
10	Centre Rene Huguenin	Saint Cloud	France	92211
11	Hopital Paul Brousse	Villejuif	France	94804
12	Azienda Sanitaria di Bolzano	Bolzano	Italy	39100
13	Universita G.D'Annunzio Di Chieti	Chieti	Italy	66100
14	Ospedale San Carlo Borromeo	Milano (Milan)	Italy	20153
15	Azienda Ospedale S. Luigi at University of Torino	Orbassano, (Torino)	Italy	10043
16	Fondazione Salvatore Maugeri	Pavia	Italy	I-27100
17	Ospedale Oncologico Regionale	RIONERO in VULTURE	Italy	I-58028
18	Istituto Regina Elena	Rome	Italy	00161
19	Istituto Clinico Beato Matteo	Vigevano	Italy	27029
20	Hospital Fernando Fonseca	Amadora	Portugal	P-2700