Comparing Capecitabine and Temozolomide in Combination to Lutetium Lu 177 Dotatate in Patients With Advanced Pancreatic Neuroendocrine Tumors, the ComPareNET Trial

This phase II trial compares capecitabine and temozolomide to lutetium Lu 177 dotatate for the treatment of pancreatic neuroendocrine tumors that have spread to other parts of the body (advanced) or are not able to be removed by surgery (unresectable). Chemotherapy drugs, such as capecitabine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and may reduce harm to normal cells. The purpose of this study is to find out whether capecitabine and temozolomide or lutetium Lu 177 dotatate may kill more tumor cells in patients with advanced pancreatic neuroendocrine tumors. The primary and secondary objectives of the study: PRIMARY OBJECTIVE: I. To determine the differences in median progression-free survival (PFS) for lutetium Lu 177 dotatate peptide receptor radionuclide therapy (PRRT) when compared to capecitabine and temozolomide (CAPTEM) in patients with locally advanced or metastatic progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs). SECONDARY OBJECTIVES: I. To evaluate and compare the overall survival (OS) of patients receiving lutetium Lu 177 dotatate versus (vs.) CAPTEM. II. To evaluate and compare time to response, time to maximum response, and overall response rates (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 between both arms. III. To evaluate and compare duration of response and time to progression among both arms. IV. To evaluate and compare treatment related toxicities between the arms. V. To compare global health status/quality of life as measured with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 from baseline through 18 months between patients with pNET treated with lutetium Lu 177 dotatate PRRT versus capecitabine and temozolomide. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive lutetium Lu 177 dotatate intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples prior to registration, on days 1 and 29 of each cycle, during post-treatment follow-up, and at progressive disease, withdrawal or removal from study. Patients undergo PET prior to registration, and CT and/or magnetic resonance imaging (MRI) prior to registration and then every 3 months until progression. ARM II: Patients receive capecitabine orally (PO) twice daily (BID) days 1-14 of each cycle and temozolomide PO once daily (QD) on days 10-14 of each cycle. Treatment repeats every 4 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples prior to registration, on day 1 of each cycle, and at progressive disease, withdrawal, or removal from study. Patients undergo PET prior to registration, and CT and/or MRI prior to registration and then every 3 months until progression.