FLOX in Combination With Cetuximab in First-line Treatment of Colorectal Cancer

Study Overview
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Brief Summary
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The main objective of this trial is to explore the effect of combining an established chemotherapy regimen (FLOX), based on 5-fluorouracil, folinic acid, and oxaliplatin (Eloxatin®), with the EGF receptor antibody cetuximab (Erbitux®) in first-line treatment of metastatic colorectal cancer. The trial will investigate two regimens of FLOX plus cetuximab, in which FLOX is given continuously or intermittently, compared to standard FLOX without cetuximab.

Official Title
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5-Fluorouracil/Folinate/Oxaliplatin (Eloxatin) (FLOX Regimen), Given Continuously or Intermittently, in Combination With Cetuximab (Erbitux), in First-line Treatment of Metastatic Colorectal Cancer. A Phase III Multicenter Trial.

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: FLOX (5-fluorouracil/folinic acid/oxaliplatin)
* Drug: FLOX (5-fluorouracil/folinic acid/oxaliplatin) and Cetuximab
* Drug: FLOX (5-fluorouracil and folinic acid and oxaliplatin) intermittently and maintenance cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histology and staging disease: Histological proven adenocarcinoma of the colon or rectum; At least one measurable metastatic disease If only one metastatic lesion and no S-CEA elevation, histology is mandatory; Availability of tumour sample for EGFR assessment. General conditions: Age >18 and < 75 years; WHO performance status: life expectancy of more than 3 months; Adequate haematological function Adequate renal and hepatic functions Written informed consent Exclusion Criteria: Prior therapy: No prior chemotherapy for advanced/metastatic disease; No adjuvant chemotherapy the last 6 months before inclusion; No previous oxaliplatin; Prior or current history: No current indication for resection with a curative intent; No evidence of CNS metastasis; No current infection, unresolved bowel obstruction or subobstruction, uncontrolled Crohn's disease or ulcerative colitis; No current history of chronic diarrhoea; No peripheral neuropathy; No other serious illness or medical conditions (including contraindication to 5 FU e.g.: angor, myocardial infarction within 6 months, contraindications to monoclonal antibodies); No past or concurrent history of malignant neoplasm other than colorectal adenocarcinoma within the past five years, except curatively treated non melanoma skin cancer or in situ carcinoma of the cervix; Concomitant treatments: No concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; No concurrent treatment with any other anti-cancer therapy; Other: Not pregnant, no breast feeding Fertile patients must use adequate contraceptives Not include patients clearly intending to withdraw from the study if not randomised in the willing arm or patients who cannot be regularly followed up for psychological, social, familiar or geographic reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>FLOX: 5-fluorouracil/folinic acid/oxaliplatin; Nordic Regimen; given continuosly | Drug: FLOX (5-fluorouracil/folinic acid/oxaliplatin)<br>* FLOX every 2nd week<br>|
| Experimental: B<br>FLOX: 5-fluorouracil/folinic acid/oxaliplatin and cetuximab | Drug: FLOX (5-fluorouracil/folinic acid/oxaliplatin) and Cetuximab<br>* FLOX every 2nd week Cetuximab weekly<br>|
| Experimental: C<br>FLOX given intermittently and maintenance cetuximab | Drug: FLOX (5-fluorouracil and folinic acid and oxaliplatin) intermittently and maintenance cetuximab<br>* FLOX every 2nd week for 8 cycles. Stop of FLOX until progression then FLOX is reintroduced. Cetuximab weekly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare efficacy, as measured by time to disease progression, of treatment with cetuximab in combination with the FLOX regimen compared to FLOX alone, in first- line treatment of patients with metastatic cororectal cancer |  | Every 4th cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure response rates, response duration, secondary surgical curative resection frequency, safety profile, overall survival and quality of life in the treatment groups. |  | Every 2nd week (safety profile) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic colorectal cancer, FLOX, Cetuximab