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

NCT00479752 | Completed Phase 2

• 1 other identifier: CECOG /CORE 1.2.002
• Study Type: interventional
• Target: 151
• Locations: 12 countries
• Sites: 23

Brief Summary

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

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• The primary endpoint of the trial is: • Objective response (CR/PR), as assessed by RECIST criteria

  Objective response (partial or complete) will be assessed using RECIST criteria. The objective response rate (defined as the rate of subjects with complete response (CR) or partial response (PR)) will be estimated and associated exact two-sided 95% confidence limit (Clopper-Pearson) will be calculated. In addition to the estimates within each treatment group odds ratios and associated 95% CI will be calculated using the Cochran Mantel-Haenszel procedure.

  The objective response rate - defined as the rate of subjects with complete response (CR) or partial response (PR)

Secondary Outcomes (1)

• • Progression Free Survival (PFS) • Overall survival • Safety/Adverse events Safety

  he rate of subjects with complete response (CR) or partial response (PR)

Study Arms (2)

A

ACTIVE COMPARATOR

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.

Drug: FOLFOX4 (Oxaliplatin), Cetuximab

B

ACTIVE COMPARATOR

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.

Drug: FOLFOX4 (Oxaliplatin), Cetuximab

Interventions

FOLFOX4 (Oxaliplatin), Cetuximab 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.

A; B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Central European Cooperative Oncology Group: lead

Study Sites (24)

LKH Leoben, Abt. für Innere Medizin

Leoben, Styria, 8700, Austria

Location

Medical University of Vienna

Vienna, Austria

Location

Institute of Oncology Sarajevo

Sarajevo, Bosnia and Herzegovina

Location

SBALO National Oncology Center

Sofia, 1754, Bulgaria

Location

University Hospital Centre Rijeka

Rijeka, 51000, Croatia

Location

University Hospital for Tumors

Zagreb, Croatia

Location

University Hospital Rebro

Zagreb, Croatia

Location

Noth estonian Regional Oncology Hospital

Tallinn, 13419, Estonia

Location

AHEPA Hospital University Hospital Papageorgiou

Athens, Greece

Location

General Hospital of Athens

Athens, Greece

Location

Semmelweis Univ. Radiology Clinic

Budapest, 1082, Hungary

Location

National Medical Center

Budapest, 1135, Hungary

Location

Markusovsy Hospital

Szombathely, 39700, Hungary

Location

Meir Medical Center

Kfar Saba, Israel

Location

Oncology Division Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

P. Stradins University Hospital

Riga, 1020, Latvia

Location

latvian Center of Oncology

Riga, 1079, Latvia

Location

Institutul Oncologic Bucuresti

Bucharest, Romania

Location

Institutul Oncologic Ion Chiricuta

Cluj-Napoca, Romania

Location

Institute of Oncology and Radiology of Serbia

Belgrade, 11000, Serbia

Location

Institute of Oncology of Vojvodina

Kamenitz, 21204, Serbia

Location

National Cancer Institute

Bratislava, 83310, Slovakia

Location

National Institute of Oncology

Bratislava, Slovakia

Location

Institute of Oncology

Ljubljana, 1000, Slovenia

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tudor Ciuleanu, Prof. Dr.

  Institutul Oncologic of Cluj

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2007
• First Posted: May 28, 2007
• Study Start: January 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: November 1, 2015
• Last Updated: February 18, 2016

Record last verified: 2016-02

Locations

BO (1); GR (2); CR (3); BU (1); AU (2); LA (2); IL (2); HU (3); SL (2); ES (1); RO (2); SE (2)