Activity and Safety of Everolimus+Octreotide LAR+Metformin in Advanced Pancreatic Well-differentiated NETs (MetNET1)
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|ClinicalTrials.gov Identifier: NCT02294006|
Recruitment Status : Unknown
Verified November 2014 by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
Recruitment status was: Recruiting
First Posted : November 19, 2014
Last Update Posted : November 19, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Well Differentiated Pancreatic Endocrine Tumor||Drug: Everolimus plus Octreotide LAR plus Metformin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Activity and Safety of Everolimus in Combination With Octreotide LAR and Metformin in Patients With Advanced Pancreatic Well-differentiated Neuroendocrine Tumors (pWDNETs): a Phase II, Open, Monocentric, Prospective Study|
|Study Start Date :||June 2014|
|Estimated Primary Completion Date :||June 2017|
|Estimated Study Completion Date :||June 2017|
|Experimental: everolimus+octreotide LAR+metformin||
Drug: Everolimus plus Octreotide LAR plus Metformin
- to determine the progression free survival rate (PFS) at 12 months from the first drug administration in patients with advanced pancreatic neuroendocrine tumors [ Time Frame: 1 year ]progression free survival rate at 12th month of treatment, according to RECIST criteria version 1.0
- to determine the safety and tolerability of the combination of Everolimus, Octreotide LAR and Metformin as measured according to the National cancer Institute-Common Toxicity Criteria v. 3.0 guidelines [ Time Frame: 1 year ]safety is measured according to the National cancer Institute-Common Toxicity Criteria v. 3.0 guidelines
- to determine the overall survival of the combination of Everolimus, Octreotide LAR and Metformin. [ Time Frame: 3 years ]overall survival is defined as the time interval between enrollment and the date of the death from any cause.
- to determine the response rate of the combination of Everolimus, Octreotide LAR and Metformin. [ Time Frame: 1 year ]response rate is defined as the percentage of patients presenting objective responce of the disease, according to RECIST Criteria version 1.0.
- to determine the biochemical response of the combination of Everolimus, Octreotide LAR and Metformin. [ Time Frame: 1 year ]the biochemical response is defined as the impact of study treatment on general neuroendocrine tumors biomarkers, Chromogranine A and Enolase neuron specific and circulating plasma IL6, IL8 and IGF-1 levels.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02294006
|Contact: Filippo De Braud, MDfirstname.lastname@example.org|
|Contact: Sara Pusceddu, MDemail@example.com|
|Fondazione IRCCS Istituto Tumori Milano||Recruiting|
|Milano, Italy, 20133|
|Contact: Sara Pusceddu, MD firstname.lastname@example.org|
|Principal Investigator:||Filippo De Braud, MD||INT MILANO|
|Principal Investigator:||Roberto Buzzoni, MD||INT MILANO|
|Principal Investigator:||Sara Pusceddu, MD||INT MILANO|