PRIMARY OBJECTIVE:~I. To evaluate the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of combination triapine + lutetium Lu 177 dotatate and standard of care lutetium Lu 177 dotatate alone.~SECONDARY OBJECTIVE:~I. To evaluate progression-free survival (PFS) in study and control arm.~EXPLORATORY OBJECTIVES:~I. To evaluate plasma hPG80 as a biomarker of treatment response. II. To evaluate plasma deoxyribonucleosides as a biomarker of triapine resistance.~III. Collect plasma for circulating deoxyribonucleic acid (DNA) (ctDNA) assessment.~OUTLINE: Patients are randomized to 1 of 2 groups.~GROUP I: Patients receive lutetium Lu 177 dotatate intravenously (IV) on study. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial.~GROUP II: Patients receive lutetium Lu 177 dotatate IV and triapine orally (PO) on study. Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
This phase II trial compares the effect of adding triapine to lutetium Lu 177 dotatate versus lutetium Lu 177 dotatate alone (standard therapy) in shrinking tumors or slowing tumor growth in patients with neuroendocrine tumors that have spread from where they first started (primary site) to other places in the body (metastatic). Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for deoxyribonucleic acid synthesis and cell growth. Lutetium Lu 177 dotate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177 dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Giving triapine in combination with lutetium Lu 177 dotatate may be more effective at shrinking tumors or slowing tumor growth in patients with metastatic neuroendocrine tumors than the standard therapy of lutetium Lu 177 dotatate alone.