Safety and Efficacy Study of Combination Therapy With Cetuximab and FOLFOX4 in Patients With Colorectal Cancer

NCT ID: NCT00202787

Last Updated: 2013-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2009-02-28

Brief Summary

The purpose of this study is to determine confirmed objective response rate to combination therapy with cetuximab and FOLFOX4 or FOLFOX4 alone in patients with CRC and non-resectable hepatic metastases

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

FOLFOX-4+cetuximab

Group Type: EXPERIMENTAL

FOLFOX-4+cetuximab

Intervention Type: DRUG

Cetuximab; Weekly administration of Cetuximab IV (initial infusion of 400 mg/m2 for 120 minutes followed by subsequent maintenance doses of 250 mg/m2 for 60 minutes);

FOLFOX-4: Every two week Oxaliplatin; 85 mg/m2 ; day 1 Folinic acid; 200 mg/m2 ; day 1 and 2 5-FU ; Bolus 400 mg/m2 + CI 600 mg/m2 22 h day 1 and 2

2

FOLFOX-4

Group Type: ACTIVE_COMPARATOR

FOLFOX-4

Intervention Type: DRUG

FOLFOX-4: Every two week Oxaliplatin; 85 mg/m2 ; day 1 Folinic acid; 200 mg/m2 ; day 1 and 2 5-FU ; Bolus 400 mg/m2 + CI 600 mg/m2 22 h day 1 and 2

Interventions

FOLFOX-4+cetuximab

Cetuximab; Weekly administration of Cetuximab IV (initial infusion of 400 mg/m2 for 120 minutes followed by subsequent maintenance doses of 250 mg/m2 for 60 minutes);

FOLFOX-4: Every two week Oxaliplatin; 85 mg/m2 ; day 1 Folinic acid; 200 mg/m2 ; day 1 and 2 5-FU ; Bolus 400 mg/m2 + CI 600 mg/m2 22 h day 1 and 2

Intervention Type: DRUG

FOLFOX-4

FOLFOX-4: Every two week Oxaliplatin; 85 mg/m2 ; day 1 Folinic acid; 200 mg/m2 ; day 1 and 2 5-FU ; Bolus 400 mg/m2 + CI 600 mg/m2 22 h day 1 and 2

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent.
• Men and women < 75 years
• Histologically confirmed diagnosis of CRC
• Metastatic colorectal carcinoma with exclusive non-resectable hepatic metastases, due to fulfillment of one of the following criteria:

1. Number of hepatic metastases > or= 4;

2. Size of one or more hepatic metastases > 5 cm diameter;

3. Vascular involvement and/or poor site that prevent complete resection of hepatic disease and/or require resection with the remaining liver mass less than 25-30% of functional liver.

• Presence of at least one lesion detectable by two-dimensional measurement.
• Karnofsky functional status >or=70% at the time of enrollment in study
• Life expectancy greater than 3 months.
• Patients must not have received chemotherapy for advanced/metastatic disease.
• Patients with the following characteristics will be enrolled:

1. Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with disease-free period > 6 months following conclusion of treatment.

2. Recurrence after surgical and/or radiotherapy treatment without adjuvant systemic treatment.

3. De novo diagnosis of disease.

• Proper liver function, defined by aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < or = 2.5 x ULN (< or = 5 x ULN if there are hepatic metastases) and total bilirubin count < 1.5 x ULN.
• Proper kidney function, defined as serum creatinine < 1.5 x ULN.
• Proper hematological function, defined as neutrophil count > or = 1.5 x 109/l , platelets > or = 100 X 109/l and hemoglobin > or = 9 g/dl.
• Effective birth control method for men as well as women if there is possibility of pregnancy

Exclusion Criteria

• Documented or suspected cerebral and/or leptomeningeal metastases.
• Metastasis in any other non-hepatic site, including extrahepatic lymph node metastases.
• Surgery (excluding biopsy for diagnosis) and/or radiotherapy within 4 weeks prior to enrollment in the study.
• Participation in another clinical trial with medication in the past 30 days.
• Chronic, concomitant administration of systemic immunotherapy, chemotherapy, hormone therapy or any other investigational drug.
• Prior malignant tumour in past 5 years, except history of basal cell skin carcinoma or pre-invasive cervical carcinoma.
• Any investigational drug during the 4 weeks prior to enrolment.
• Prior administration of monoclonal antibodies, EGFR signal transduction inhibitors or EGFR-targeted treatment.
• Prior participation in study in which treatment with cetuximab can be assigned (whether or not treatment with cetuximab is received)
• Acute or subacute intestinal occlusion or history of inflammatory intestinal disease.
• Evidence of grade 3 or 4 allergic reaction to any of the treatment components.
• Clinically relevant peripheral neuropathy.
• Clinically relevant myocardial disease or history of myocardial infarction in the past 12 months.
• Known abuse of alcohol / drugs, Legal incapacity or limited legal capacity.
• Any medical or psychological disorder which, in the opinion of the investigator, does not allow the patient to conclude the study or sign the informed consent.
• Pregnant or nursing woman

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Albert Abad

Role: STUDY_CHAIR

Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)

Locations

Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)

Madrid, , Spain

Countries

Spain

Other Identifiers

eudract-number: 2004-001700-12

Identifier Type: -

Identifier Source: secondary_id

TTD-04-02

Identifier Type: -

Identifier Source: org_study_id