Metformin and 5-fluorouracil for Refractory Colorectal Cancer.

Sponsor

Instituto do Cancer do Estado de São Paulo (Other)

Overall Status

Completed

CT.gov ID

NCT01941953

Collaborator

(none)

Enrollment

Location

Arm

27.9

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Metformin and Fluorouracil	Phase 2

Detailed Description

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)

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin and Flourouracil	Drug: Metformin and Fluorouracil metformin 850mg PO BID plus 5FU 425mg/m2 + leucovorin 50mg IV weekly

Arm

Intervention/Treatment

Experimental: Metformin and Flourouracil

Drug: Metformin and Fluorouracil

metformin 850mg PO BID plus 5FU 425mg/m2 + leucovorin 50mg IV weekly

Outcome Measures

Primary Outcome Measures

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

Progression-free Survival [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.]
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.
Overall Survival [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]
defined as time from first dose of treatment until death, with date of last visit being considered censorship
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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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