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

Study Overview
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Brief Summary
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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.

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

Conditions
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Well-differentiated Neuroendocrine Tumors

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: METFORMIN<br>850mg of metformin every 12 hours. | Drug: Metformin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroendocrine Tumors, The Mammalian Target of Rapamycin (mTOR), metformin