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Activity and Safety of Everolimus+Octreotide LAR+Metformin in Advanced Pancreatic Well-differentiated NETs

NCT02294006 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 26

Last updated 2021-09-09

No results posted yet for this study

Summary

Abnormal PI3K-Akt-mTOR (mammalian target of rapamycin) pathway signaling and autocrine activation of the mTOR pathway, mediated through insulin-like growth factor 1 (IGF1), has been implicated in the proliferation of pNET ( primitive neuroectodermal tumor) cells. Everolimus ,an mTOR inhibitor (a central regulator of growth/proliferation, cellular metabolism and angiogenesis) has shown antitumor benefit in pNETs alone and in combination with Octreotide LAR in RADIANT-1 and RADIANT-3 studies.

Despite EVE-based phase II/III trials improve progression-free survival (PFS) for pNETs, they are limited to significantly prolong overall survival (OS). Metformin has recently shown some anti-cancer activity, both in vitro and in vivo studies by antisecretory properties to decrease insulin and IGF1 levels; and by antitumor effect due to AMPK (adenosine monophosphate kinase) activation and consequently inhibition to TSC1(tuberous sclerosis complex 1) -2/mTOR complex, mediated to LKB1 oncogene expression. The investigators retrospective experience, despite in a limited group of pWDNET, highlights the role of MET to improve clinical benefit in diabetic pts receiving EVE-OCT (octreotide) combination.

This study will investigate the antiproliferative potential of MET in combination with EVE and OCT in pWDNETs. MetNET1 prospective trial (EudraCT 2014-000888-41) may be helpful to either confirm or discard these preliminary findings.

The main objective of this study is to evaluate progression free survival rate at 12 months of treatment. The secondary objectives are safety, overall survival, response rate evaluation.

A sub-study analysis will evaluate circulant biomarkers levels (IL 6, IGF1) in blood samples.

Conditions

  • Well Differentiated Pancreatic Endocrine Tumor

Interventions

DRUG

Everolimus plus Octreotide LAR plus Metformin

Everolimus plus Octreotide LAR plus Metformin

Sponsors & Collaborators

  • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

    lead OTHER

Principal Investigators

  • Filippo De Braud, MD · INT MILANO

  • Roberto Buzzoni, MD · INT MILANO

  • Sara Pusceddu, MD · INT MILANO

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-06-30
Primary Completion
2021-06-30
Completion
2021-10-31

Countries

  • Italy

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02294006 on ClinicalTrials.gov