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

Colorectal Cancer Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00479752
• Other study ID #: CECOG /CORE 1.2.002
• Status: Completed
• Phase: Phase 2
• First received: May 25, 2007
• Last updated: February 17, 2016
• Start date: January 2008
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: Central European Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and Women
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: November 2015
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Austria	LKH Leoben, Abt. für Innere Medizin	Leoben	Steiermark
Austria	Medical University of Vienna	Vienna
Bosnia and Herzegovina	Institute of Oncology Sarajevo	Sarajevo
Bulgaria	SBALO National Oncology Center	Sofia
Croatia	University Hospital Centre Rijeka	Rijeka
Croatia	University Hospital for Tumors	Zagreb
Croatia	University Hospital Rebro	Zagreb
Estonia	Noth estonian Regional Oncology Hospital	Tallin
Greece	AHEPA Hospital University Hospital Papageorgiou	Athens
Greece	General Hospital of Athens	Athens
Hungary	National Medical Center	Budapest
Hungary	Semmelweis Univ. Radiology Clinic	Budapest
Hungary	Markusovsy Hospital	Szombathely
Israel	Meir Medical Center	Kfar Saba
Israel	Oncology Division Sourasky Medical Center	Tel Aviv
Latvia	latvian Center of Oncology	Riga
Latvia	P. Stradins University Hospital	Riga
Romania	Institutul Oncologic Bucuresti	Bucuresti
Romania	Institutul Oncologic Ion Chiricuta	Cluj Napoca
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
Serbia	Institute of Oncology of Vojvodina	Sremska Kamenica
Slovakia	National Cancer Institute	Bratislava
Slovakia	National Institute of Oncology	Bratislava
Slovenia	Institute of Oncology	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
Central European Cooperative Oncology Group

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Secondary	• 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)	Yes