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

A PHASE II PILOT STUDY OF METFORMIN TREATMENT IN PATIENTS WITH WELL-DIFFERENTIATED NEUROENDOCRINE TUMORS

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.

Study Overview

• Status: Unknown
• Conditions: Well-differentiated Neuroendocrine Tumors
• Intervention / Treatment: Drug: Metformin

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 01246-000
      • Recruiting
      • Instituto do Cancer do Estado de Sao Paulo
      • Contact: João Glasberg, MD; Phone Number: 55 11 38932000; Email: pesquisa.clinica@icesp.org.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: METFORMIN; 850mg of metformin every 12 hours.	Drug: Metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	After 180 days of treatment.

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo
• Investigators: Principal Investigator: João Glasberg, MD, Instituto do Cancer do Estado de Sao Paulo

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: July 7, 2014
• First Submitted That Met QC Criteria: October 30, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Estimate): October 31, 2014
• Last Update Submitted That Met QC Criteria: October 30, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: metformin; Neuroendocrine Tumors; The Mammalian Target of Rapamycin (mTOR)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: NP 515/2014