DRAFT: RAMSETE trial of everolimus (RAD001) in the treatment of silent (nonfunctioning) advanced neuroendocrine tumors.

Abstract

TPS208 Background: Nonfunctioning (nf) neuroendocrine tumors (NETs) do not hypersecrete biogenic amines and peptidic hormones in the blood, ie, they are nonsyndromic. Nf NETS represent at least 50% of gastroenteropancreatic NETs. Nf NETs may have symptoms due to tumor mass effect, such as abdominal pain and jaundice. Surgery is the only curative option but is limited to early well-differentiated disease. For inoperable advanced disease, there are currently no standard tumor control therapies. Everolimus is an oral inhibitor of the mammalian target of rapamycin (mTOR; a central regulator of cell growth and proliferation, cellular metabolism, and angiogenesis) and interrupts insulin-like growth factor/phosphatidylinositol 3-kinase signaling that is integral to NETs growth. Everolimus plus octreotide LAR showed promising efficacy in a phase II study in pts with pancreatic NETs (Yao 2009). Few studies have specifically focused on nf NETs at other primary sites (eg, bronchial, rectal, etc). The RAMSETE (RAD001 in Advanced and Metastatic Silent Neuro-Endocrine Tumours in Europe)clinical trial is examining the efficacy and safety of daily oral everolimus therapy for the treatment of advanced nonsyndromic NET pts, excluding pts with pancreatic NETs. Methods: RAMSETE is a single-arm, multicenter, single- stage phase II trial (target enrollment: 60 pts) of everolimus (10 mg/day) monotherapy treating pts with advanced nonsyndromic NETs, not including pancreatic NETs or poorly differentiated NETs. Pts may have received 0-3 prior systemic treatments and must have progressed within 12 months prior to enrollment. Study initiation was June 24, 2009; accrual is expected to finish in mid-2010. Everolimus will continue until tumor progression. The primary efficacy endpoint is the proportion of pts with complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) criteria. Secondary endpoints include disease control rate (CR + PR + SD [stable disease]), biochemical response rate based on the tumor marker chromogranin A, progression-free survival, overall survival, and safety. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis