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Metformin and 5-fluorouracil for Refractory Colorectal Cancer.

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Metformin and Fluorouracil
Sponsored by
Instituto do Cancer do Estado de São Paulo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Metformin, Metastatic Colorectal Cancer, Fluorouracil

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Instituto Do Cancer Do Estado de São Paulo

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metformin and Flourouracil

Arm Description

Outcomes

Primary Outcome Measures

Disease Control Rate according to RECIST 1.1

Secondary Outcome Measures

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.
Overall Survival
defined as time from first dose of treatment until death, with date of last visit being considered censorship
Adverse Events

Full Information

First Posted
September 4, 2013
Last Updated
April 6, 2015
Sponsor
Instituto do Cancer do Estado de São Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT01941953
Brief Title
Metformin and 5-fluorouracil for Refractory Colorectal Cancer.
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 Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto do Cancer do Estado de São Paulo

4. Oversight

Data Monitoring Committee
No

5. 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.
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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Metformin, Metastatic Colorectal Cancer, Fluorouracil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metformin and Flourouracil
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Metformin and Fluorouracil
Intervention Description
metformin 850mg PO BID plus 5FU 425mg/m2 + leucovorin 50mg IV weekly
Primary Outcome Measure Information:
Title
Disease Control Rate according to RECIST 1.1
Time Frame
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 Measure Information:
Title
Progression-free Survival
Description
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.
Time Frame
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.
Title
Overall Survival
Description
defined as time from first dose of treatment until death, with date of last visit being considered censorship
Time Frame
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
Title
Adverse Events
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Instituto Do Cancer Do Estado de São Paulo
City
Sao Paulo
ZIP/Postal Code
01246-000
Country
Brazil

12. IPD Sharing Statement

Learn more about this trial

Metformin and 5-fluorouracil for Refractory Colorectal Cancer.

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