Safety and Efficacy of Folfox4 + Weekly Cetuximab vs Folfox 4+Biweekly Cetuximab by Metastatic Colorectal Cancer

NCT ID: NCT00479752

Last Updated: 2016-02-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2015-11-30

Brief Summary

To assess the efficacy of FOLFOX4 in combination with cetuximab, weekly and FOLFOX4 in combination with cetuximab, biweekly.

Detailed Description

This multicenter randomized phase II study will enroll approximately 150 patients with metastatic Colorectal Cancer. Patients are randomized in Arm A(FOLFOX4 in combination with weekly Cetuximab) or Arm B (FOLFOX4 in combination with biweekly Cetuximab). Both efficacy and safety data will be collected. The investigator will assess response to treatment every 8 weeks based on the imaging.

Following permanent treatment cessation, patients will be followed-up for survival.

Conditions

Colorectal Cancer

Study Design

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

Study Groups

A

FOLFOX4:

• Oxaliplatin 85 mg/m² d1
• Leucovorin 200 mg/m² d1+d2, followed by
• Bolus 5FU 400 mg/m², followed by
• Infusional 5FU 600 mg/m²,over 22 hours, every 2 weeks

Cetuximab is administered to arm A of the study as an infusion with initial dose 400 mg/m² in week 1 followed by weekly doses of 250 mg/m².

Group Type: ACTIVE_COMPARATOR

FOLFOX4 (Oxaliplatin), Cetuximab

Intervention Type: DRUG

Arm A FOLFOX4:

• Oxaliplatin 85 mg/m² d1
• Leucovorin 200 mg/m² d1+d2, followed by
• Bolus 5FU 400 mg/m², followed by
• Infusional 5FU 600 mg/m²,over 22 hours, every 2 weeks

Cetuximab is administered to arm A of the study as an infusion with initial dose 400 mg/m² in week 1 followed by weekly doses of 250 mg/m².

Arm B FOLFOX4:

• Oxaliplatin 85 mg/m² d1
• Leucovorin 200 mg/m² d1+d2, followed by
• Bolus 5FU 400 mg/m² , followed by
• Infusional 5FU 600 mg/m², over 22 hours, every 2 weeks

Cetuximab is administered to arm B of the study as infusions of 500 mg/m² every two weeks.

B

FOLFOX4:

• Oxaliplatin 85 mg/m² d1
• Leucovorin 200 mg/m² d1+d2, followed by
• Bolus 5FU 400 mg/m² , followed by
• Infusional 5FU 600 mg/m², over 22 hours, every 2 weeks

Cetuximab is administered to arm B of the study as infusions of 500 mg/m² every two weeks.

Group Type: ACTIVE_COMPARATOR

FOLFOX4 (Oxaliplatin), Cetuximab

Intervention Type: DRUG

Arm A FOLFOX4:

• Oxaliplatin 85 mg/m² d1
• Leucovorin 200 mg/m² d1+d2, followed by
• Bolus 5FU 400 mg/m², followed by
• Infusional 5FU 600 mg/m²,over 22 hours, every 2 weeks

Cetuximab is administered to arm A of the study as an infusion with initial dose 400 mg/m² in week 1 followed by weekly doses of 250 mg/m².

Arm B FOLFOX4:

• Oxaliplatin 85 mg/m² d1
• Leucovorin 200 mg/m² d1+d2, followed by
• Bolus 5FU 400 mg/m² , followed by
• Infusional 5FU 600 mg/m², over 22 hours, every 2 weeks

Cetuximab is administered to arm B of the study as infusions of 500 mg/m² every two weeks.

Interventions

FOLFOX4 (Oxaliplatin), Cetuximab

Arm A FOLFOX4:

• Oxaliplatin 85 mg/m² d1
• Leucovorin 200 mg/m² d1+d2, followed by
• Bolus 5FU 400 mg/m², followed by
• Infusional 5FU 600 mg/m²,over 22 hours, every 2 weeks

Cetuximab is administered to arm A of the study as an infusion with initial dose 400 mg/m² in week 1 followed by weekly doses of 250 mg/m².

Arm B FOLFOX4:

• Oxaliplatin 85 mg/m² d1
• Leucovorin 200 mg/m² d1+d2, followed by
• Bolus 5FU 400 mg/m² , followed by
• Infusional 5FU 600 mg/m², over 22 hours, every 2 weeks

Cetuximab is administered to arm B of the study as infusions of 500 mg/m² every two weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent
• Male or female ≥ 18 years of age
• Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
• Metastatic colorectal carcinoma not suitable for curative-intent resection- Availability of tumor sample (or able and willing to provide tumor sample) for EGFR assessment
• Presence of at least one lesion measurable unidimensionally by CT scan or MRI. (Target lesion(s) must not lie within an irradiated area)
• Karnofsky performance status of > 80 at study entry
• Leucocytes ≥ 3.0 x 10 9/L and neutrophils ≥1.5 x 10 9/L, platelets ≥ 100 x 10 9/L, and hemoglobin ≥ 9 g/dL.
• Bilirubin ≥ 1.5 x ULN
• ASAT and ALAT ≤ 2.5 x ULN (≤5 x ULN if liver metastasis are present)
• Serum creatinine ≤ 1.5 x ULN

Exclusion Criteria

• Brain metastasis (known or suspected)
• Previous chemotherapy for metastatic disease. Prior adjuvant chemotherapy is allowed if the chemotherapy treatment free interval is > 6 months.
• Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry
• Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
• Any investigational agent(s) within 4 weeks prior to entry
• Previous exposure to EGFR-pathway targeting therapy
• Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months
• Acute or subacute intestinal occlusion or history of inflammatory bowel disease
• Pre-existing neuropathy > grade 1. In case of prior oxaliplatin containing adjuvant chemotherapy: pre-existing neuropathy ≥ 1.
• Known grade 3 or 4 allergic reaction to any of the components of the treatment.
• Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial)
• Pregnancy or lactation
• Inadequate contraception (male or female patients) if of childbearing or procreational potential
• Known drug abuse/ alcohol abuse
• Legal incapacity or limited legal capacity
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

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

Sponsors

Central European Cooperative Oncology Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tudor Ciuleanu, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Institutul Oncologic of Cluj

Locations

LKH Leoben, Abt. für Innere Medizin

Leoben, Styria, Austria

Medical University of Vienna

Vienna, , Austria

Institute of Oncology Sarajevo

Sarajevo, , Bosnia and Herzegovina

SBALO National Oncology Center

Sofia, , Bulgaria

University Hospital Centre Rijeka

Rijeka, , Croatia

University Hospital for Tumors

Zagreb, , Croatia

University Hospital Rebro

Zagreb, , Croatia

Noth estonian Regional Oncology Hospital

Tallinn, , Estonia

AHEPA Hospital University Hospital Papageorgiou

Athens, , Greece

General Hospital of Athens

Athens, , Greece

Semmelweis Univ. Radiology Clinic

Budapest, , Hungary

National Medical Center

Budapest, , Hungary

Markusovsy Hospital

Szombathely, , Hungary

Meir Medical Center

Kfar Saba, , Israel

Oncology Division Sourasky Medical Center

Tel Aviv, , Israel

P. Stradins University Hospital

Riga, , Latvia

latvian Center of Oncology

Riga, , Latvia

Institutul Oncologic Bucuresti

Bucharest, , Romania

Institutul Oncologic Ion Chiricuta

Cluj-Napoca, , Romania

Institute of Oncology and Radiology of Serbia

Belgrade, , Serbia

Institute of Oncology of Vojvodina

Kamenitz, , Serbia

National Cancer Institute

Bratislava, , Slovakia

National Institute of Oncology

Bratislava, , Slovakia

Institute of Oncology

Ljubljana, , Slovenia

Countries

Austria; Bosnia and Herzegovina; Bulgaria; Croatia; Estonia; Greece; Hungary; Israel; Latvia; Romania; Serbia; Slovakia; Slovenia

Other Identifiers

CECOG /CORE 1.2.002

Identifier Type: -

Identifier Source: org_study_id