Leucovorin, Fluorouracil, Cetuximab, and Oxaliplatin in Treating Patients With Stage IV Colorectal Cancer and Liver Metastases That Cannot Be Removed by Surgery

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00544349

Collaborator

(none)

Enrollment

Locations

6.4

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) and giving them together with cetuximab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving leucovorin together with fluorouracil, cetuximab, and oxaliplatin works in treating patients with stage IV colorectal cancer and liver metastases that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Biological: cetuximab Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the efficacy of this regimen by the measurement of objective response rate (RECIST criteria).

Secondary

Determine the toxicity of this regimen.
Evaluate the duration of tumor response.
Determine the duration and rate of tumor control.
Determine the rate of secondary resectability of hepatic metastases.
Evaluate progression-free survival
Determine rate of progression of the tumor.
Determine overall survival.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1 hour, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours. Patients also receive oxaliplatin by hepatic arterial infusion over 2 hours. Treatment continues for at least 3 months in the absence of disease progression or unacceptable toxicity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Non-Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study Evaluating the Effectiveness of the Association of Chemotherapy LV5FU2 Simplified and Cetuximab With Intra-arterial Hepatic Chemotherapy Using Oxaliplatin in Patients With Colorectal Cancer and Nonresectable Hepatic Metastases

Study Start Date :

Oct 1, 2006

Actual Primary Completion Date :

May 1, 2011

Outcome Measures

Primary Outcome Measures

Efficacy: objective tumor response rate (RECIST criteria) []

Secondary Outcome Measures

Toxicity as assessed by NCI CTCAE v3.0 []
Duration of response []
Duration and rate of tumor control []
Secondary resectability of hepatic metastases []
Progression-free survival []
Overall survival []
Tumor progression rate []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed primary cancer of the colon or rectum
Isolated hepatic metastases
Not amenable to curative resection or requirement for complex and or larger (i.e., > 4 liver segments) liver resection
Measurable disease (RECIST criteria)
Original tumor must be (or have been) removed

PATIENT CHARACTERISTICS:

Inclusion criteria:

WHO performance status 0-1
Life expectancy > 3 months
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Creatinine ≤ 1.5 times normal
Bilirubin ≤ 1.5 times upper limit of normal
Transaminases ≤ 5 times normal
Not pregnant or nursing
Fertile patients must use effective contraception

Exclusion criteria:

Contraindication or allergy grade 3-4 to any components of the study drugs
Peripheral neuropathy
Intestinal occlusion or subocclusion or prior inflammatory intestinal disease
Severe cardiac disease including any of the following:
Symptomatic coronary disease
Myocardial infarction in the past 6 months
New York Heart Association grade II-IV cardiac insufficiency
Severe arrhythmia (even if treated)
Active or uncontrolled infection
Other concurrent serious disorder
Severe uncontrolled medical condition
Other malignancy within the past 5 years or concurrently except basal cell skin cancer or carcinoma in situ of the cervix
Study impossible due to psychological, geographical, or social reasons
Prisoners or patients under guardianship

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

Prior chemotherapy except adjuvant chemotherapy comprising fluorouracil, leucovorin calcium, capecitabine, oxaliplatin, irinotecan hydrochloride, and/or bevacizumab (completed > 6 months ago if oxaliplatin- or irinotecan-based)
Prior epidermal growth factor (EGF), monoclonal antibody inhibiting transduction of EGF receptor (EGFR), or any other treatment targeting the EGFR
Other concurrent anticancer immunotherapy, chemotherapy, or hormone therapy
Participation in another study in the past 30 days

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital Saint Andre	Bordeaux	France	33075
2	Centre Regional Francois Baclesse	Caen	France	14076
3	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon	France	21079
4	CHU Pitie-Salpetriere	Paris	France	75651
5	Centre Eugene Marquis	Rennes	France	35062
6	Hopital Paul Brousse	Villejuif	France	94804
7	Institut Gustave Roussy	Villejuif	France	F-94805