FLOX + Cetuximab (Erbitux®) for Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor

Study Overview
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Brief Summary
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The Nordic FLOX-regime consists of a combination of bolus 5-FU, leukovorin and oxaliplatin (Eloxatin®). Cetuximab (Erbitux®) is an antibody against the epidermal growth factor receptor (EGFR). The combination of FLOX and weekly Erbitux has been investigated in the Nordic VII study where 571 patients were randomized to FLOX (regime A) or FLOX + Erbitux (regime B or C). Effect-data has not yet been published but the combination is well tolerated, and other studies have shown that Erbitux administered with chemotherapy seem to be more efficient than chemotherapy alone. The main purpose with this study is to investigate the effect of FLOX and Erbitux given every second week as first line treatment for patients with metastatic colorectal cancer and K-RAS wildtype tumor. The latest accessible data regarding treatment towards EGFR and K-RAS mutations shows that patients with K-RAS wildtype responds better to treatment than patients with K-RAS mutations.

Official Title
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FLOX + Cetuximab (Erbitux®): First Line Treatment for Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor, A Phase II Study

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Cetuximab (Erbitux)
* Drug: Oxaliplatin (Eloxatin) + Fluorouracil + folinic acid


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 lesion according to RECIST criteria If only one metastatic lesion, histology is mandatory Mutation level: Tumor tissue (primary or metastasis) typological classified as K-RAS wildtype in codon 12 and 13 in exon 1 at real-time PCR General conditions: Age >18 and < 75 years WHO performance status ≤ 2; life expectancy of more than 3 months Adequate haematological function: (Hb ≥ 6.2 μmol/d, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L) Adequate renal and hepatic functions: total bilirubin ≤ 1.5 upper normal limit, creatinine ≤ 1.25 × upper normal limit, ALAT ≤ 3 x upper normal limits, and ≤ 5 x upper normal limits in case of liver metastases Written informed consent prior to randomisation must be obtained and documented according to the local regulatory requirements Other: Fertile patients must use adequate contraceptives Exclusion Criteria: Prior therapy: Prior chemotherapy for advanced/metastatic disease Adjuvant chemotherapy must have ended > 6 months before inclusion Prior treatment with Eloxatin Prior treatment with Erbitux or other treatment to EGFR Prior or current history: Current indication for resection with a curative intent Evidence of CNS metastasis Current infection, unresolved bowel obstruction or subobstruction, uncontrolled Crohn's disease or ulcerative colitis Current history of chronic diarrhea Peripheral neuropathy Other serious illness or medical conditions (including contraindication to 5 FU e.g.: angor, myocardial infarction within 6 months, contraindications to monoclonal antibodies) 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: Concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation Concurrent treatment with any other anti-cancer therapy Other: Pregnant or breast feeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cetuximab (Erbitux)|500 mg/m² every second week, intravenous infusion, 8 cycles|
|Drug: Oxaliplatin (Eloxatin) + Fluorouracil + folinic acid|Given in combination day 1 and 2, every second week, 8 cycles|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erbitux, Colorectal cancer, Oxaliplatin, Flox, Fluorouracil + folinic acid, K-RAS