Metformin and 5-fluorouracil for Refractory Colorectal Cancer.

Study Overview
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Brief Summary
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This is a phase II trial to evaluate efficacy and safety of Metformin and Fluorouracil in patients with metastatic colorectal cancer (CRC) who have progressed after Oxaliplatin and Irinotecan based chemotherapy.

Detailed Description
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Primary Outcomes Measures: - Disease control Rate at 8 weeks according to RECIST 1.1 (Tumor response was defined as the percentage of patients with complete response, partial response or stable disease as best overall response). Secondary Outcome Measures: Progression-free Survival Overall Survival Adverse Events (assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0)

Official Title
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Phase II Study of Metformin and 5-fluorouracil in Patients With Advanced Colorectal Cancer Previously Treated With Oxaliplatin and Irinotecan Based Chemotherapy.

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Metformin and Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histological diagnosis of metastatic colorectal adenocarcioma previously treated with at least two lines of chemotherapy (oxaliplatin and irinotecan regimens) if mutated KRAS or treated with at least 3 lines of chemotherapy (oxaliplatin, irinotecan and cetuximab) if KRAS wild type. Disease progression according to radiological or clinical assessment. Measurable disease. ECOG Performance 0-1. Age above 16 years. Normal organic function as defined for the following criteria: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 times the upper normal limit of the local laboratory (LSN-LL); Total serum bilirubin ≤ 2.0 x ULN-LL; Absolute neutrophil count ≥ 1,500 / mm3; Platelet count ≥ 100,000 / mm3; Hemoglobin ≥ 8.0 g / dl; Serum creatinine ≤ 1.5 x ULN-LL Written informed consent before enrollment Exclusion Criteria Diabetic patients taking metformin. Patients already treated with mTOR inhibitors. Hypersensitivity to metformin, renal or hepatic impairment or other conditions that predispose to lactic acidosis. History of acute myocardial infarction in the last 6 months Serious illness or psychiatric condition. Current participation in other protocols with experimental drugs. Suspicion of dihidropirimida dehydrogenase(DPD)deficiency. Presence of active infection. No ability to ingest food orally. Patients with metastatic disease to CNS. Patients who underwent major surgery in the last 4 weeks. Patients who received chemotherapy in the last three weeks. Patients who underwent radiotherapy in the last 2 weeks or who received radiotherapy in the target lesion, if this is the only target lesion. Patients using oral anticoagulation (warfarin). Pregnant or lactating patients

Ages Eligible for Study
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Minimum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin and Flourouracil<br> | Drug: Metformin and Fluorouracil<br>* metformin 850mg PO BID plus 5FU 425mg/m2 + leucovorin 50mg IV weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate according to RECIST 1.1 |  | From randomization of the first subject until the database cut-off approximately 12 months later (01Nov2012 up to 01Nov2015). Tumor assessed at 8 week intervals | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | defined as time from randomization to death from any cause, or even radiological detection/or clinical of disease progression, increased CEA will not be considered isolated progression. | From randomization of the first subject until the database cut-off approximately 12 months later (01Nov2012 up to 01Nov2015). Tumor assessed at 4 week intervals. | 
| Overall Survival | defined as time from first dose of treatment until death, with date of last visit being considered censorship | From randomization of the first subject until the database cut-off approximately 12 months later (01Nov2012 up to 01Nov2015). Tumor assessed at 4 week intervals | 
| Adverse Events |  | From randomization of the first subject until the database cut-off approximately 12 months later (01Nov2012 up to 01Nov2015). Tumor assessed at 4 week intervals. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Metastatic Colorectal Cancer, Fluorouracil