Clinical trial NCT00039208: Combination Chemotherapy in Treating Patients With Colorectal Cancer
Official title: Time Finding Study of Chronomodulated Irinotecan, 5 Fluorouracil, Leucovorin and Oxaliplatin as First or Second Chemotherapy Line Against Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy
Secondary outcomes:
measure: 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
measure: Peak delivery time for CPT11 activity over the first 3 courses
measure: Peak delivery time for CPT11 tolerability and efficacy over the first 6 courses
measure: Severe toxic events assessed by CTC v2.0 after each course of chemotherapy
measure: Progression-free survival
measure: Overall survival
Other outcomes:
Locations:
city: Charleroi
country: Belgium
facility: Centre Hospitalier Notre Dame - Reine Fabiola
city: Liege
country: Belgium
facility: Clinique Saint-Joseph
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Namur
country: Belgium
facility: Clinique Sainte Elisabeth
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer-La Tourelle
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Limoges
country: France
facility: Centre Hospital Regional Universitaire de Limoges
city: Paris
country: France
facility: Hopital Saint-Louis
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Bolzano
country: Italy
facility: Azienda Sanitaria di Bolzano
city: Chieti
country: Italy
facility: Universita G.D'Annunzio Di Chieti
city: Milano (Milan)
country: Italy
facility: Ospedale San Carlo Borromeo
city: Orbassano, (Torino)
country: Italy
facility: Azienda Ospedale S. Luigi at University of Torino
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: RIONERO in VULTURE
country: Italy
facility: Ospedale Oncologico Regionale
city: Rome
country: Italy
facility: Istituto Regina Elena
city: Vigevano
country: Italy
facility: Istituto Clinico Beato Matteo
city: Amadora
country: Portugal
facility: Hospital Fernando Fonseca
Study officials:
affiliation: Istituti Fisioterapici Ospitalieri - Roma
name: Carlo Garufi, MD
role: STUDY_CHAIR
References:
citation: 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.