Treatment of neuroendocrine tumors (NETs) with combination of everolimus and lu-177 radiolabeled somatostatin analogue.

Abstract

TPS502 Background: Treatment of Grade 1 and 2 NET is complex and involves surgical, Locoregional and systemic modalities depending on the manifestations as well as extent of disease. Of the emerging new systemic modalities are everolimus and radiolabelled somatostatin analogue. everolimus is FDA approved for advanced pancreatic NET whereas radiolabelled somatostatin analogue is still not standard therapy in the USA. However, it is gaining popularity especially in Europe as effective systemic therapy for somatostatin receptor positive tumors. Subclinical animal model research showed synergistic effect of the combination of everolimus and the Lu-177 radiolabeled somatostatin analogue. The goal of this study is to assess the safety and efficacy of the combination of Everolimus and the intravenous radiolabeled Lu-177 DOTATOC Therapy in the treatment of unresectable G1-2 neuroendocrine tumors of all gastrointestinal, lung and pancreatic origins. Methods: This is a phase 1 – 2 study. The phase 1 part involves finding the maximum tolerating dose (DLT) of everolimus and accordingly to recommend dose for the phase II part. The second part is a standard phase II trial assessing the efficacy and toxicity of the regimen at the recommended dose. A total of 30 patients will be enrolled, based on the expected response of the combination to be 20% with power of 80 and type 1 of.05, compared to the known everolimus alone overall all response of 5%. In phase 1, three patients will be treated with 5mg daily with expansion to six patients if one of the three patients experienced DLT. If DLT occurred in none of three or no more than one of six patients, everolimus dose will be escalated to 10 mg and will be considered the recommended dose for phase 2 part. Otherwise, everolimus dose will be kept at 5 mg daily and will be considered the recommended dose for phase II part. DLT in more than two of six patients will be considered unacceptable, and the trial will be closed because of high toxicity.