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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00544349
• Other study ID #: CDR0000564063
• Secondary ID: FRE-IGR-CHOICEIG
• Status: Completed
• Phase: Phase 2
• First received: October 13, 2007
• Last updated: May 14, 2011
• Start date: October 2006

Study information

• Verified date: July 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Biological:
• cetuximab

Drug:
• fluorouracil

• leucovorin calcium

• oxaliplatin

Locations

Country	Name	City	State
France	Hopital Saint Andre	Bordeaux
France	Centre Regional Francois Baclesse	Caen
France	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon
France	CHU Pitie-Salpetriere	Paris
France	Centre Eugene Marquis	Rennes
France	Hopital Paul Brousse	Villejuif
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: objective tumor response rate (RECIST criteria)			No
Secondary	Toxicity as assessed by NCI CTCAE v3.0			Yes
Secondary	Duration of response			No
Secondary	Duration and rate of tumor control			No
Secondary	Secondary resectability of hepatic metastases			No
Secondary	Progression-free survival			No
Secondary	Overall survival			No
Secondary	Tumor progression rate			No