Safety of lanreotide 120 mg ATG in combination with metformin in patients with advanced well-differentiated gastro-intestinal (GI) or lung carcinoids. A pilot, one-arm, open-label, prospective study: The MetNET-2 trial

Date

08 Oct 2016

Session

Poster Display

Presenters

Filippo De Braud

Citation

Annals of Oncology (2016) 27 (6): 136-148. 10.1093/annonc/mdw369

Authors

F.G.M. De Braud1, R. Buzzoni2, L. Concas2, D. Femia2, N. Prinzi2, M. Milione3, E. Tamborini3, F. Perrone3, G. Lo Russo4, C. Vernieri2, I. Pulice2, F. Piras2, G. Dinoi2, S. Pusceddu2

Author affiliations

  • 1 Division Of Oncology-university Of Milan, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2 Medical Oncology Department, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 3 Department Of Pathology And Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 4 Oncology Department, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
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Background

In the CLARINET trial, lanreotide (LAN) 120 mg resulted in a 53% reduction in the risk of death or disease progression, compared with placebo, in GI-NET patients. Several studies have identified diabetic patients (pts) as having increased risk for the development of cancer and have associated metformin (MET) treatment with a decrease of cancer risk. MET may have anti-proliferative activity due to its ability to decrease insulin and IGF1 levels; in addition, it promotes AMPK activation and TSC1-2/mTOR inhibition. Our retrospective experience in a large group of pancreatic NET, has suggested that MET may provide additional clinical benefit in diabetic pts receiving everolimus and/or somatostatin analogues.

This study evaluates the safety of LAN 120 mg in combination with MET in pts with advanced well-differentiated GI or lung carcinoids.

Trial design

Methods: Pts with advanced GI or lung carcinoids will receive a combination of LAN 120 mg/month and MET 2550 mg/day, until progression or inacceptable toxicity. Radiological progression will be assessed every 4 months. The primary objective is to evaluate the incidence of adverse events (AEs) and severe AEs (SAEs). A 1-stage Hern design will be used. The null hypothesis that the SAEs rate related to the treatment is [25%] will be tested against a one-sided alternative. 20 pts with available tissue specimens will be enrolled. The null hypothesis will be rejected if ≤2 pts will experience a severe toxicity. This design yields a type I error rate of 10% and power of 85% when the true toxicity rate is ≥5%. The expression of 111 genes potentially involved in the pathways related to MET (e.g., LKB1, TP53, KRAS, IGF1R, VEGFR, PDGFR, AKT, PIK3CA, PTEN, mTOR) will be assessed by a target NGS approach. Other endpoints include TTP and RR.

Results: In March 2016, the trial received institutional ethic board approval and in April 2016 the enrollment was started (EudraCT 2015-004626-34). Recruitment will be completed in April 2017.

Conclusions: This study will investigate the safety of the combination of LAN 120 mg and MET and the correlation between tumor mutations and response to this therapy.

Clinical trial identification

Protocol EUDRACT Number: 2015-004626-34 approved by Ethical committee of Fondazione IRCCS Istituto Tumori Milan on 8 March 2016

Legal entity responsible for the study

Fondazione IRCCS Istituto Tumori Milano

Funding

Fondazione IRCCS Istituto Tumori Milano

Disclosure

S. Pusceddu: Ipsen, Novartis, Italfarmaco, Pfizer. All other authors have declared no conflicts of interest.

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