PRIMARY OBJECTIVE:~I. To evaluate the effect of lutetium Lu 177 dotatate (177Lu-DOTATATE) versus (vs.) everolimus on progression-free survival (PFS) in patients with metastatic/unresectable midgut neuroendocrine tumour (NET) who have progressed following previous peptide receptor radionuclide therapy (PRRT).~SECONDARY OBJECTIVES:~I. To evaluate the toxicity and safety of 177Lu-DOTATATE and everolimus. II. To determine the effect of 177Lu-DOTATATE vs. everolimus on overall response rate (ORR).~III. To evaluate the effect of 177Lu-DOTATATE vs. everolimus on overall survival (OS).~IV. To evaluate post progression survival (PPS) and time to second objective disease progression (PFS2) for patients randomized to Arm 2 of the study and crossed over to Arm 1 at time of objective progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.~V. To evaluate the effect of 177Lu-DOTATATE vs. everolimus on patient quality of life (QoL).~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM I: Patients receive 177Lu-DOTATATE intravenously (IV) on study. Patients also undergo computed tomography (CT) scan and collection of blood samples on study.~ARM II: Patients receive everolimus orally (PO) on study. Patients whose cancer worsens may receive re-treatment with 177Lu-DOTATATE IV on study. Patients also undergo CT scan and collection of blood samples on study.
This phase II trial compares the effect of retreatment with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) to treatment with everolimus in patients with midget neuroendocrine tumors that have spread from where it first started (primary site) to other places in the body (metastatic) and that cannot be removed by surgery (unresectable). PRRT involves treatment with a radioactive substance that is linked to a peptide receptor so that it will attach to a specific cell type when injected into the body. 177Lu-DOTATATE, a PRRT drug, may increase the length of time until worsening of disease by 8 months compared to the usual approach. Everolimus treats cancer by stopping cancer cells from reproducing and by decreasing blood supply to the cancer cells. Everolimus prevents transplant rejection by decreasing the activity of the immune system. Giving 177Lu-DOTATATE may work better in shrinking and stabilizing tumors in patients with neuroendocrine tumors.