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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Central European Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00479752
First received: May 25, 2007
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Colorectal Cancer
Drug: FOLFOX4 (Oxaliplatin), Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Central European Cooperative Oncology Group:

Primary Outcome Measures:
  • The primary endpoint of the trial is: • Objective response (CR/PR), as assessed by RECIST criteria [ Time Frame: The objective response rate - defined as the rate of subjects with complete response (CR) or partial response (PR) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • • Progression Free Survival (PFS) • Overall survival • Safety/Adverse events Safety [ Time Frame: he rate of subjects with complete response (CR) or partial response (PR) ] [ Designated as safety issue: Yes ]
    Secondary objectives are the estimation of differences in PFS and overall survival.


Enrollment: 151
Study Start Date: January 2008
Estimated Study Completion Date: November 2014
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00479752

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

No publications provided

Responsible Party: Central European Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00479752     History of Changes
Other Study ID Numbers: CECOG /CORE 1.2.002
Study First Received: May 25, 2007
Last Updated: May 20, 2014
Health Authority: Austria: Federal Ministry for Health and Women

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 25, 2014