Trials / Recruiting

RecruitingNCT05773274

Comparing Retreatment of 177Lu-DOTATATE PRRT Versus the Usual Treatment in Patients With Metastatic Unresectable Gastroenteropancreatic Neuroendocrine Tumors, NET RETREAT Trial

NET RETREAT: A Phase II Study of 177 Lutetium-DOTATATE Retreatment vs. Everolimus or Sunitinib or Cabozantinib in Metastatic/Unresectable Gastroenteropancreatic Neuroendocrine Tumours

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 100 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

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, sunitinib, or cabozantinib in patients who have previously received 177Lu-DOTATATE for gastroenteropancreatic neuroendocrine tumor (GEPNET) 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 tumor cells. When this radioactive peptide is injected into the body, it binds to a specific receptor found on some tumor cells. The radioactive peptide builds up in these cells and helps kill the tumor 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 GEPNET 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 tumor cells from reproducing and by decreasing blood supply to the tumor cells. Sunitinib and cabozantinib, block certain proteins, which may help keep tumor cells from growing. They may also prevent the growth of new blood vessels that tumors need to grow. Sunitinib malate is a type of tyrosine kinase inhibitor and a type of antiangiogenesis agent. Retreating with 177Lu-DOTATATE may work better than everolimus, sunitinib or cabozantinib in shrinking or stabilizing tumors in patients with metastatic and unresectable GEPNET who were previously treated with 177Lu-DOTATATE.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the effect of lutetium Lu 177 dotatate (177Lu-DOTATATE) versus (vs.) everolimus or sunitinib (for pancreatic neuroendocrine \[NET\] patients only) or cabozantinib (United States \[US\] patients only) on progression-free survival (PFS) in patients with metastatic/unresectable GEPNET who have progressed following previous peptide receptor radionuclide therapy (PRRT). SECONDARY OBJECTIVES: I. To evaluate the toxicity and safety of 177Lu-DOTATATE and everolimus or sunitinib (for pancreatic neuroendocrine NET patients only) or cabozantinib (US patients only). II. To determine the effect of 177Lu-DOTATATE vs. everolimus or sunitinib (for pancreatic neuroendocrine NET patients only) or cabozantinib (US patients only) on overall response rate (ORR). III. To evaluate the effect of 177Lu-DOTATATE vs. everolimus or sunitinib (for pancreatic neuroendocrine NET patients only) or cabozantinib (US patients only) 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 or sunitinib (for pancreatic neuroendocrine NET patients only) or cabozantinib (US patients only) on patient quality of life (QoL). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive 177Lu-DOTATATE intravenously (IV) over 30 minutes 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/or magnetic resonance imaging (MRI) and collection of blood samples while on study. ARM II: Patients receive everolimus orally (PO) on a daily basis (QD), sunitinib PO QD or cabozantinib PO 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/or MRI and collection of blood samples while on study. After completion of study treatment, patients are followed up every 12 weeks until objective disease progression and then every 6 months until death.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
DRUG	Cabozantinib	Given PO
PROCEDURE	Computed Tomography	Undergo CT scan
DRUG	Everolimus	Given PO
DRUG	Lutetium Lu 177 Dotatate	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Sunitinib	Given PO

Timeline

Start date: 2024-01-12
Primary completion: 2029-04-30
Completion: 2029-04-30
First posted: 2023-03-17
Last updated: 2026-04-15

Locations

36 sites across 2 countries: United States, Canada

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05773274. Inclusion in this directory is not an endorsement.