3534 - HORMONET: Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression

Background

Patients (pts) with advanced neuroendocrine tumors (NET) represent an unmet medical need, what motivates the development of new treatments. Prior retrospective study conducted by our group showed that among 96 NET, immunohistochemistry (IHC) expression for estrogen (ER) and progesterone receptors (PR) were observed in 20.8% and 18.8% of cases, respectively. Additionally, an old clinical trial (Mortel C, 1984) suggested antitumor effects of estrogen/progesterone-directed therapies in NET pts. Yet the effects of an antiestrogen agent in NET pts whose tumor express ER and/or PR are unknown. Hence we will conduct a clinical trial to test the efficacy of tamoxifen in ER/PR positive NET pts.

Trial design

Single-arm phase II multicenter trial of tamoxifen 20mg PO continuously until intolerance and/or tumor progression. Eligible pts must be ≥ 18 years old, have histologically confirmed advanced, irresectable well-differentiated lung or gastroeteropancreatic NET, IHC expression of ER and/or PR ≥ 1%, documented progression in the prior 12 months, measurable disease, prior treatments with standard therapies and/or no indication to start new treatment due to lack of access, risk of toxicities or without clinical indication (patients who meet criteria for watchful waiting may be included), ECOG 0-2, adequate organ function. Main exclusion criteria are: aggressive disease requiring cytotoxic therapy, use of oral anticoagulants, previous history of deep vein thrombosis or pulmonary embolism in the last 12 months, postmenopausal vaginal bleeding with no defined etiology. The primary endpoint is disease control rate (DCR) at week 24 as per RECIST 1.1. Secondary endpoints are progression-free survival, biochemical response, response rate. Exploratory evaluations: circulating tumor cells kinetics (qualitative and quantitative) and PET-CT gallium-68 intake intensity variation (at baseline and at week 24). Sample size assumptions: the H0 is DCR at week 24 of 50% and H1, 70%; with a type I error of 10%, power of 80% and attrition rate of 30%, the final sample size will be 22 pts.

Clinical trial identification

NCT03870399.

Editorial acknowledgement

Legal entity responsible for the study

Rachel Riechelmann.

Funding

AC Camargo Cancer Center.

Disclosure

M. Barros: Honoraria (self): Novartis. J.F. Rego: Honoraria (self): Novartis. R.P. Riechelmann: Honoraria (self): Novartis. All other authors have declared no conflicts of interest.