A Pilot Study of Metformin Treatment in Patients With Well-differentiated Neuroendocrine Tumors

Phase 2

• Conditions: Well-differentiated Neuroendocrine Tumors
• Interventions: Drug: Metformin

• Registration Number: NCT02279758
• Lead Sponsor: Instituto do Cancer do Estado de São Paulo

Brief Summary

Neuroendocrine tumors are rare but recent data showed a relevant increase in its incidence. The Mammalian Target of Rapamycin (mTOR), one of most important area of research, has demonstrated be a therapeutic target in these tumors. The metformin has demonstrate in preclinical studies having an antineoplastic action by inhibiting the mTOR pathway, and may be an alternative treatment for this disease.

Eligible patients for this study should have metastatic gastroenteropancreatic neuroendocrine tumors well differentiated (grade 1 or grade 2) and will be treated with metformin 850 mg every 12 hours, and each cycle will consist of 30 days. After 180 days of treatment the efficacy of metformin under the control of disease progression will be evaluated. As a secondary outcome the investigator will check the patient adherence to the treatment, the control of patient symptoms with functioning neuroendocrine tumor, and disease free survival. Also will be performed an analysis of immunohistochemical expression of mTOR pathway proteins of these patients.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-07-07
• Status Verified: 2014-10
• Study First Submitted QC: 2014-10-30
• Last Update Submitted: 2014-10-30
• Study First Posted: 2014-10-31
• Last Update Posted: 2014-10-31
• Primary Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Metastatic well-differentiated neuroendocrine tumor grade 1 or 2 with histological confirmation;
• Performance status according to Eastern Cooperative Oncology Group (ECOG) 0 to 2;
• Able to take pills;
• Age ≥ 16 years;
• Ability to Provide Written Informed Consent;
• Adequate organ function;

Read More

Exclusion Criteria

• Patient with out of control severe hormonal syndrome;
• Diabetic patients under metformin treatment, or those who have received treatment with metformin within 3 months;
• Patient with hypersensitivity to biguanides, kidney or liver failure, or other conditions that predispose to lactic acidosis;
• History of severe clinical or psychiatric illness, that would prevent participation in the study by clinical judgment;
• Patients who participate in other protocol with experimental drugs;
• Patients under any kind of active infection;
• Patients who have received chemotherapy within 3 weeks;
• Patients pregnant or lactating;
• Diabetic patients who require higher dose of metformin 850mg x 2 daily;

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
METFORMIN	Metformin	850mg of metformin every 12 hours.

Primary Outcome Measures

Name	Time	Method
Disease free survival	After 180 days of treatment.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events Related to Metformin Measured of Safety and Tolerability	Assessments will be performed until 180 days after treatment initiation	Clinical evaluation of metformin related toxicity will be assessed at each medical visit (once a month).
Clinical benefit	Assessments will be performed until 180 days after treatment initiation.	Clinical benefit will be measured using CTCAE version 4.03 for analysis of adverse events presented by patients.
Biochemical response	Assessment will be performed at day 90 and 180 of treatment.	Biochemical response defined by tumor markers.
Evaluation of patient's glycemic profile	Assessment will be performed at day 90 and day 180 of treatment.

Trial Locations

Locations (1)

Instituto do Cancer do Estado de São Paulo; 🇧🇷 Sao Paulo, SP, Brazil