Clinical trial NCT01941953: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Metformin
Metastatic Colorectal Cancer
Fluorouracil
Lead sponsor: Instituto do Cancer do Estado de São Paulo
Sponsor class: OTHER
First posted: 2013-09-13
Enrollment: 50
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)

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

Primary outcomes:
measure: Disease Control Rate according to RECIST 1.1
timeFrame: 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 outcomes:
measure: Progression-free Survival
timeFrame: 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.
measure: Overall Survival
timeFrame: 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
measure: Adverse Events
timeFrame: 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.
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Instituto Do Cancer Do Estado de São Paulo
Study officials:
References: