Metastatic Midgut Neuroendocrine Tumor Clinical Trial
Official title:
NET RETREAT: A Phase II Study of 177 Lutetium-DOTATATE Retreatment vs. Everolimus in Metastatic/Unresectable Midgut NET
This phase II trial compares the effect of retreatment with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) to the usual approach of treatment with everolimus in patients who have previously received 177Lu-DOTATATE for midgut neuroendocrine tumor (NET) that has spread from where it first started (primary site) to other places in the body (metastatic) and that cannot be removed by surgery (unresectable). PRRT is a type of radiation therapy for which a radioactive chemical is linked to a peptide (small protein) that targets cancer cells. When this radioactive peptide is injected into the body, it binds to a specific receptor found on some cancer cells. The radioactive peptide builds up in these cells and helps kill the cancer cells without harming normal cells. In this trial 177Lu-DOTATATE is used for PRRT. 177Lu-DOTATATE PRRT may increase the length of time until worsening of the midgut NET compared to the usual approach. Everolimus is in a class of medications called kinase inhibitors. It is also a type of angiogenesis inhibitor. Everolimus works by stopping cancer cells from reproducing and by decreasing blood supply to the cancer cells. Retreating with 177Lu-DOTATATE may work better than everolimus in shrinking or stabilizing tumor in patients with metastatic and unresectable NET who were previously treated with 177Lu-DOTATATE.
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) every 8 weeks (Q8W). Treatment repeats for two cycles in the absence of disease progression or unacceptable toxicities. Patients also undergo computed tomography (CT) scan and collection of blood samples while on study. ARM II: Patients receive everolimus orally (PO) on a daily basis (QD). Treatment continues in the absence of disease progression or unacceptable toxicities. Patients whose cancer worsens may cross over to ARM I. Patients also undergo CT scan and collection of blood samples while on study. ;