Safety and Efficacy Study of mFOLFOX-6 Plus Cetuximab for 8 Cycles Followed by mFOLFOX-6 Plus Cetuximab or Single Agent Cetuximab as Maintenance Therapy in Patients With Metastatic Colorectal Cancer and WT KRAS Tumours

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and safety of the combination of mFOLFOX-6 plus cetuximab for 8 cycles followed by mFOLFOX-6 plus cetuximab or single agent (s/a) cetuximab as maintenance therapy in patients (pts) with metastatic colorectal cancer (mCRC).

Official Title
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Phase-II, Randomized, Multicentre Pilot Study to Evaluate the Safety and Efficacy of the Treatment With mFOLFOX-6 Plus Cetuximab Versus Initial Treatment With mFOLFOX-6 Plus Cetuximab (for 8 Cycles), Followed by Maintenance With Cetuximab Alone as First-line Treatment in Patients With Metastatic Colorectal Cancer (mCRC) and Wild-type KRAS Tumours

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: mFOLFOX-6 + cetuximab until disease progression or early withdrawal.
* Drug: 8 cycles of mFOLFOX-6 + cetuximab, followed by cetuximab alone until disease progression or early withdrawal.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Patients of an age ≥ 18 years and < 71 Patients with an ECOG performance status ≤ 2 Confirmed histological diagnosis of colorectal carcinoma with metastatic disease and wild-type KRAS. Presence of at least one target lesion that is measurable one-dimensionally (not located in an irradiated region). Life expectancy greater than 12 weeks. First evidence of chemotherapy-naïve metastatic disease. Adjuvant chemotherapy is allowed if it has been more than 6 months since the treatment was finished and there have been no signs of disease progression, neither during treatment nor during the 6 months following its completion. Adequate medullar reserve: Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Haemoglobin ≥ 9 g/dL Adequate renal function: Creatinine clearance > 30 mL/min, calculated using the Cockroff-Gault formula, or a serum creatinine < 2 mg/dL or 177 umol/L An adequate liver function: ASAT (SGOT) and ALAT (SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if there are liver metastases). Total bilirubin < 1.5 x ULN. Alkaline phosphatase ≤ 2.5 x ULN ( ≤ 5 x ULN in the case of liver metastases or ≤ 10 x ULN in the case of bone metastases) Exclusion Criteria: To have received prior systemic treatment for the metastatic disease Diagnosis or suspicion of brain or leptomeningeal metastases Major surgery or radiotherapy (except for antalgic surgery that does not include measurable target lesions) during the 4 weeks prior to inclusion in the study. Previous administration of monoclonal antibodies, agents inhibiting EGFR signal transduction or EGFR-targeted treatment. Participation in another clinical trial with drugs within the previous 30 days. Neoplasm in the 2 years prior to entering the study, except for non-melanoma skin carcinoma or in situ cervix carcinoma. Evidence of previous acute hypersensitivity reaction of any degree to any of the treatment's components. Clinically relevant peripheral neuropathy. Signs and symptoms, at the moment of entering the study, of acute or subacute bowel obstruction. A history of an acute episode of ischemic heart disease (angina or acute myocardial infarction) within the previous 12 months or an elevated risk of heart failure decompensation or uncontrolled arrhythmia. Serious active infection, including active tuberculosis and HIV diagnosis. Chronic immunological or hormonal treatment, except for hormone replacement treatment at physiological doses. Known drug or alcohol abuse. Legal incapacity or limited legal capacity. Pregnancy or breastfeeding. Premenopausal women must have a negative pregnancy test in urine or blood before entering the trial. Patients and their partners must take contraceptive measures (hormonal, barrier, or abstinence) if the possibility of conception exists, during the study and for 3 months after the end of the treatment thereof. Any geographical or social circumstance or any medical or psychological alteration that, in the investigator's opinion, will not allow the patient to conclude the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Control<br>mFOLFOX-6 + cetuximab until disease progression or early withdrawal. | Drug: mFOLFOX-6 + cetuximab until disease progression or early withdrawal.<br>* Treatment regimen: mFOLFOX-6, day 1, every two weeks; OXALIPLATIN 85 mg/m2; FOLINIC ACID 400 mg/m2; 5-FU 400 mg/m2 IV bolus; 5-FU 2400 mg/m2 continuous infusion for 46 hours Cetuximab weekly. Cetuximab 400 mg/m2 the first time the treatment is administered; 250 mg/m2 for subsequent administrations.<br>|
| Experimental: Experimental<br>8 cycles of mFOLFOX-6 + cetuximab, followed by cetuximab alone until disease progression or early withdrawal. | Drug: 8 cycles of mFOLFOX-6 + cetuximab, followed by cetuximab alone until disease progression or early withdrawal.<br>* Treatment regimen. mFOLFOX-6. day 1 every two weeks. OXALIPLATIN 85 mg/m2; FOLINIC ACID 400 mg/m2; 5-FU 400 mg/m2 IV bolus; 5-FU 2400 mg/m2 continuous infusion for 46 hours Cetuximab weekly. Cetuximab 400 mg/m2 the first time the treatment is administered; 250 mg/m2 for subsequent administrations.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | 2010-2014 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 2010-2014 | 
| rate of objective responses |  | 2010-2014 | 
| disease's resectability (R0) |  | 2010-2014 | 
| evaluate hypomagnesaemia as a predictive factor in the treatment's efficacy |  | 2010-2014 | 
| Adverse events |  | 2010-2014 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic colorectal cancer, wild-type KRAS tumours, cetuximab, mFOLFOX-6