Metformin and 5-fluorouracil for Refractory Colorectal Cancer.

Metastatic Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01941953
• Other study ID #: NP 273/12
• Status: Completed
• Phase: Phase 2
• First received: September 4, 2013
• Last updated: April 6, 2015
• Start date: November 2012
• Est. completion date: March 2015

Study information

• Verified date: April 2015
• Source: Instituto do Cancer do Estado de São Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Metformin and Fluorouracil
metformin 850mg PO BID plus 5FU 425mg/m2 + leucovorin 50mg IV weekly

Locations

Country	Name	City	State
Brazil	Instituto Do Cancer Do Estado de São Paulo	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Instituto do Cancer do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	No
Secondary	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	No
Secondary	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.	No