Safety and Efficacy of Folfox4 + Weekly Cetuximab vs Folfox 4+Biweekly Cetuximab by Metastatic Colorectal Cancer (CORE 2)

A Randomized, Open-label Phase II Study Evaluating the Efficacy and Safety of FOLFOX4 + Weekly Cetuximab Versus FOLFOX4+ Biweekly Cetuximab as First-line Therapy in Patients With Metastatic Colorectal Cancer.

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

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: FOLFOX4 (Oxaliplatin), Cetuximab

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.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Medical University of Vienna
  • Steiermark
    • Leoben, Steiermark, Austria, 8700
      • LKH Leoben, Abt. für Innere Medizin
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina
    • Institute of Oncology Sarajevo
• Bulgaria
  • Sofia, Bulgaria, 1754
    • SBALO National Oncology Center
• Croatia
  • Rijeka, Croatia, 51000
    • University hospital centre Rijeka
  • Zagreb, Croatia
    • University Hospital Rebro
  • Zagreb, Croatia
    • University Hospital For Tumors
• Estonia
  • Tallin, Estonia, 13419
    • Noth estonian Regional Oncology Hospital
• Greece
  • Athens, Greece
    • General Hospital of Athens
  • Athens, Greece
    • AHEPA Hospital University Hospital Papageorgiou
• Hungary
  • Budapest, Hungary, 1082
    • Semmelweis Univ. Radiology Clinic
  • Budapest, Hungary, 1135
    • National Medical Center
  • Szombathely, Hungary, 39700
    • Markusovsy Hospital
• Israel
  • Kfar Saba, Israel
    • Meir Medical Center
  • Tel Aviv, Israel, 64239
    • Oncology Division Sourasky Medical Center
• Latvia
  • Riga, Latvia, 1020
    • P. Stradins University Hospital
  • Riga, Latvia, 1079
    • latvian Center of Oncology
• Romania
  • Bucuresti, Romania
    • Institutul Oncologic Bucuresti
  • Cluj Napoca, Romania
    • Institutul Oncologic Ion Chiricuta
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Oncology and Radiology of Serbia
  • Sremska Kamenica, Serbia, 21204
    • Institute of Oncology of Vojvodina
• Slovakia
  • Bratislava, Slovakia, 83310
    • National Cancer Institute
  • Bratislava, Slovakia
    • National Institute of Oncology
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Institute of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: 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.
Active Comparator: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Progression Free Survival (PFS) • Overall survival • Safety/Adverse events Safety	Secondary objectives are the estimation of differences in PFS and overall survival.	he rate of subjects with complete response (CR) or partial response (PR)

Collaborators and Investigators

• Sponsor: Central European Cooperative Oncology Group
• Investigators: Principal Investigator: Tudor Ciuleanu, Prof. Dr., Institutul Oncologic of Cluj

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 25, 2007
• First Submitted That Met QC Criteria: May 25, 2007
• First Posted (Estimate): May 28, 2007

Study Record Updates

• Last Update Posted (Estimate): February 18, 2016
• Last Update Submitted That Met QC Criteria: February 17, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Oxaliplatin; Cetuximab
• Other Study ID Numbers: CECOG /CORE 1.2.002