Clinical trial NCT00066274: Comparison of Combination Chemotherapy Regimens in Treating Patients With Metastatic Colorectal Cancer
Official title: Randomized Phase II Study Evaluating Three Chemotherapies: [Irinotecan + Oxaliplatin (Irinox)], [Irinotecan + LV5FU2] and [Oxaliplatin + LV5FU2] as First Intention Treatment in Subjects With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2003-08-07
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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 the drugs in different combinations may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying combination chemotherapy containing irinotecan and oxaliplatin to see how well it works compared to two standard combination chemotherapy regimens in treating patients with unresectable metastatic colorectal cancer.

Detailed description: OBJECTIVES:

* Compare the efficacy, in terms of response rate (partial response and complete response), of irinotecan and oxaliplatin vs irinotecan, fluorouracil, and leucovorin calcium vs oxaliplatin, fluorouracil, and leucovorin calcium in patients with metastatic colorectal cancer.
* Compare the progression-free survival of patients treated with these regimens.
* Compare the tolerability of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive irinotecan IV over 90 minutes and oxaliplatin IV over 2 hours on day 1.
* Arm II: Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2.
* Arm III: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2.

In all arms, treatment repeats every 2 weeks for 26 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months for 1 year.

Patients are followed at 2 months.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 1 year.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed colorectal carcinoma

  * Metastatic disease
* Not amenable to surgery
* Unidimensionally measurable disease
* No bone metastases
* No brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 to 75

Performance status

* WHO 0-2

Life expectancy

* At least 12 weeks

Hematopoietic

* Neutrophil count at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10 g/dL

Hepatic

* Bilirubin no greater than 1.25 times upper limit of normal (ULN) (1.5 times ULN if hepatic metastases are present)
* SGPT and SGOT no greater than 3 times ULN (5 times ULN if hepatic metastases are present)

Renal

* Creatinine no greater than 1.25 times ULN

Cardiac

* No concurrent cardiac abnormalities that would preclude study therapy

Pulmonary

* No concurrent pulmonary abnormalities that would preclude study therapy

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No chronic enteropathy
* No other prior cancer within the past 5 years except carcinoma in situ of the cervix or curatively treated basal cell skin cancer
* No concurrent severe uncontrolled infection
* No obstruction or partial obstruction that would interfere with study therapy
* No psychological, social, familial, or geographical situation that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent anticancer biological response modifiers

Chemotherapy

* No prior chemotherapy (except adjuvant chemotherapy completed more than 6 months ago)
* No prior irinotecan
* No prior oxaliplatin
* No other concurrent chemotherapy

Endocrine therapy

* No concurrent anticancer hormonal therapy

Radiotherapy

* At least 4 weeks since prior pelvic radiotherapy
* No prior abdominopelvic radiotherapy

Surgery

* At least 4 weeks since prior surgery
* No prior extensive intestinal resection (i.e., more than 1 prior hemicolectomy or extensive resection of the small intestines)

Other

* No other concurrent experimental medication
* No other concurrent anticancer therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Amilly
country: France
facility: Centre Hospitalier de L' Agglomeration Montargoise
city: Angers
country: France
facility: Pole Sante Sarthe et Loir Hopital Pierre Daguet
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Hyeres
country: France
facility: Clinique Sainte-Marguerite
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: Lille
country: France
facility: Centre Oscar Lambret
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Perigueux
country: France
facility: Polyclinique Francheville
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Roanne
country: France
facility: CHG Roanne
city: Rodez
country: France
facility: Centre Hospitalier de Rodez
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Thionville
country: France
facility: Centre Hospitalier Regional Metz Thionville
city: Vienne
country: France
facility: Centre Hospitalier General Lucien Hussel
Study officials:
affiliation: Institut Bergonié
name: Yves Becouarn, MD
role: STUDY_CHAIR
References:
citation: Becouarn Y, Senesse P, Thezenas S, Boucher E, Adenis A, Cany L, Jacob JH, Cvitkovic F, Montoto-Grillot C, Ychou M; Digestive Group of the Federation Nationale des Centres de Lutte Contre le Cancer. A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Federation Nationale des Centres de Lutte Contre le Cancer. Ann Oncol. 2007 Dec;18(12):2000-5. doi: 10.1093/annonc/mdm379. Epub 2007 Sep 4.