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

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
FOLFOX4 (Oxaliplatin), Cetuximab
Sponsored by
Central European Cooperative Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • LKH Leoben, Abt. für Innere Medizin
  • Medical University of Vienna
  • Institute of Oncology Sarajevo
  • SBALO National Oncology Center
  • University Hospital Centre Rijeka
  • University Hospital for Tumors
  • University Hospital Rebro
  • Noth estonian Regional Oncology Hospital
  • AHEPA Hospital University Hospital Papageorgiou
  • General Hospital of Athens
  • Semmelweis Univ. Radiology Clinic
  • National Medical Center
  • Markusovsy Hospital
  • Meir Medical Center
  • Oncology Division Sourasky Medical Center
  • P. Stradins University Hospital
  • latvian Center of Oncology
  • Institutul Oncologic Bucuresti
  • Institutul Oncologic Ion Chiricuta
  • Institute of Oncology and Radiology of Serbia
  • Institute of Oncology of Vojvodina
  • National Cancer Institute
  • National Institute of Oncology
  • Institute of Oncology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

A

B

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

• Progression Free Survival (PFS) • Overall survival • Safety/Adverse events Safety
Secondary objectives are the estimation of differences in PFS and overall survival.

Full Information

First Posted
May 25, 2007
Last Updated
February 17, 2016
Sponsor
Central European Cooperative Oncology Group
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1. Study Identification

Unique Protocol Identification Number
NCT00479752
Brief Title
Safety and Efficacy of Folfox4 + Weekly Cetuximab vs Folfox 4+Biweekly Cetuximab by Metastatic Colorectal Cancer
Acronym
CORE 2
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Central European Cooperative Oncology Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
151 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Description
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 Title
B
Arm Type
Active Comparator
Arm Description
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
Intervention Name(s)
FOLFOX4 (Oxaliplatin), Cetuximab
Intervention Description
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.
Primary Outcome Measure Information:
Title
The primary endpoint of the trial is: • Objective response (CR/PR), as assessed by RECIST criteria
Description
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.
Time Frame
The objective response rate - defined as the rate of subjects with complete response (CR) or partial response (PR)
Secondary Outcome Measure Information:
Title
• Progression Free Survival (PFS) • Overall survival • Safety/Adverse events Safety
Description
Secondary objectives are the estimation of differences in PFS and overall survival.
Time Frame
he rate of subjects with complete response (CR) or partial response (PR)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tudor Ciuleanu, Prof. Dr.
Organizational Affiliation
Institutul Oncologic of Cluj
Official's Role
Principal Investigator
Facility Information:
Facility Name
LKH Leoben, Abt. für Innere Medizin
City
Leoben
State/Province
Steiermark
ZIP/Postal Code
8700
Country
Austria
Facility Name
Medical University of Vienna
City
Vienna
Country
Austria
Facility Name
Institute of Oncology Sarajevo
City
Sarajevo
Country
Bosnia and Herzegovina
Facility Name
SBALO National Oncology Center
City
Sofia
ZIP/Postal Code
1754
Country
Bulgaria
Facility Name
University Hospital Centre Rijeka
City
Rijeka
ZIP/Postal Code
51000
Country
Croatia
Facility Name
University Hospital for Tumors
City
Zagreb
Country
Croatia
Facility Name
University Hospital Rebro
City
Zagreb
Country
Croatia
Facility Name
Noth estonian Regional Oncology Hospital
City
Tallin
ZIP/Postal Code
13419
Country
Estonia
Facility Name
AHEPA Hospital University Hospital Papageorgiou
City
Athens
Country
Greece
Facility Name
General Hospital of Athens
City
Athens
Country
Greece
Facility Name
Semmelweis Univ. Radiology Clinic
City
Budapest
ZIP/Postal Code
1082
Country
Hungary
Facility Name
National Medical Center
City
Budapest
ZIP/Postal Code
1135
Country
Hungary
Facility Name
Markusovsy Hospital
City
Szombathely
ZIP/Postal Code
39700
Country
Hungary
Facility Name
Meir Medical Center
City
Kfar Saba
Country
Israel
Facility Name
Oncology Division Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
P. Stradins University Hospital
City
Riga
ZIP/Postal Code
1020
Country
Latvia
Facility Name
latvian Center of Oncology
City
Riga
ZIP/Postal Code
1079
Country
Latvia
Facility Name
Institutul Oncologic Bucuresti
City
Bucuresti
Country
Romania
Facility Name
Institutul Oncologic Ion Chiricuta
City
Cluj Napoca
Country
Romania
Facility Name
Institute of Oncology and Radiology of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Institute of Oncology of Vojvodina
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
Facility Name
National Cancer Institute
City
Bratislava
ZIP/Postal Code
83310
Country
Slovakia
Facility Name
National Institute of Oncology
City
Bratislava
Country
Slovakia
Facility Name
Institute of Oncology
City
Ljubljana
ZIP/Postal Code
1000
Country
Slovenia

12. IPD Sharing Statement

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

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