Clinical trial NCT00479752: Safety and Efficacy of Folfox4 + Weekly Cetuximab vs Folfox 4+Biweekly Cetuximab by Metastatic Colorectal Cancer
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Central European Cooperative Oncology Group
Sponsor class: OTHER
First posted: 2007-05-28
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The primary endpoint of the trial is: • Objective response (CR/PR), as assessed by RECIST criteria
timeFrame: The objective response rate - defined as the rate of subjects with complete response (CR) or partial response (PR)
Secondary outcomes:
measure: • Progression Free Survival (PFS) • Overall survival • Safety/Adverse events Safety
timeFrame: he rate of subjects with complete response (CR) or partial response (PR)
Other outcomes:
Locations:
city: Leoben
country: Austria
facility: LKH Leoben, Abt. für Innere Medizin
state: Steiermark
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Sarajevo
country: Bosnia and Herzegovina
facility: Institute of Oncology Sarajevo
city: Sofia
country: Bulgaria
facility: SBALO National Oncology Center
city: Rijeka
country: Croatia
facility: University Hospital Centre Rijeka
city: Zagreb
country: Croatia
facility: University Hospital for Tumors
city: Zagreb
country: Croatia
facility: University Hospital Rebro
city: Tallin
country: Estonia
facility: Noth estonian Regional Oncology Hospital
city: Athens
country: Greece
facility: AHEPA Hospital University Hospital Papageorgiou
city: Athens
country: Greece
facility: General Hospital of Athens
city: Budapest
country: Hungary
facility: Semmelweis Univ. Radiology Clinic
city: Budapest
country: Hungary
facility: National Medical Center
city: Szombathely
country: Hungary
facility: Markusovsy Hospital
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Tel Aviv
country: Israel
facility: Oncology Division Sourasky Medical Center
city: Riga
country: Latvia
facility: P. Stradins University Hospital
city: Riga
country: Latvia
facility: latvian Center of Oncology
city: Bucuresti
country: Romania
facility: Institutul Oncologic Bucuresti
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Ion Chiricuta
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia
city: Sremska Kamenica
country: Serbia
facility: Institute of Oncology of Vojvodina
city: Bratislava
country: Slovakia
facility: National Cancer Institute
city: Bratislava
country: Slovakia
facility: National Institute of Oncology
city: Ljubljana
country: Slovenia
facility: Institute of Oncology
Study officials:
affiliation: Institutul Oncologic of Cluj
name: Tudor Ciuleanu, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: