Abstract 3626
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.