This phase IV trial evaluates how well giving standard of care (SOC) peptide receptor radionuclide therapy (PRRT) after SOC surgical removal of as much tumor as possible (debulking surgery) works in treating patients with grade 1 or 2, somatostatin receptor (SSTR) positive, gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have spread from where they first started (primary site) to the liver (hepatic metastasis). Lutetium Lu 177 dotatate is a radioactive drug that uses targeted radiation to kill tumor cells. Lutetium Lu 177 dotatate includes a radioactive form (an isotope) of the element called lutetium. This radioactive isotope (Lu-177) is attached to a molecule called dotatate. On the surface of GEP-NET tumor cells, a receptor called a somatostatin receptor binds to dotatate. When this binding occurs, the lutetium Lu 177 dotatate drug then enters somatostatin receptor-positive tumor cells, and radiation emitted by Lu-177 helps kill the cells. Giving lutetium Lu 177 dotatate after surgical debulking may better treat patients with grade 1/2 GEP-NETs
PRIMARY OBJECTIVES: I. To measure objective response rate of a combination standard of care treatment in gastroenteropancreatic neuroendocrine tumors by initiating lutetium Lu 177 dotatate within 90 days of surgical debulking. II. To assess the radiomic profile including somatostatin receptor standardized uptake values (SSTR SUV) of large and non-large tumors in study patients) III: To assess the safety and tolerability of peptide receptor radionuclide therapy (PRRT) post-surgical debulking in patients on study. IV. To assess the tumor genomic profile of large, resected tumors from patients and assess for signatures of radioresistance. OUTLINE: Patients undergo surgical debulking on day 0 and receive lutetium Lu 177 dotatate (177Lu dotatate) intravenously (IV) over 30 to 40 minutes on day 1 of each cycle. Treatment repeats every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) throughout the trial, and undergo copper Cu 64 dotatate positron emission tomography/CT (dotatate PET/CT) during screening and on study. After completion of study treatment, patients are followed up at 30-37 days after last dose and then every 3 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Undergo surgical debulking
Given by IV
Undergo Computed Tomography
Undergo Magnetic Resonance Imaging
Given by IV
Undergo Positron Emission Tomography
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
RECRUITINGSomatostatin receptor standardized uptake values (SSTR SUV)
SSTR SUV (not limited to but including measures such as SSTR SUV max, SSTR SUV mean) will be estimated for the patients undergoing post-operative research dotatate scans and compared to values from peptide receptor radionuclide therapy (PRRT) eligibility-conferring dotatate scans in these same patients. These quantitative analytics will be performed by central review. Changes in SSTR SUV values will be analyzed with summary statistics.
Time frame: Up to 2 years
Progression-free survival
Will be estimated by the Kaplan-Meier method.
Time frame: From the start of PRRT to the date the patient progresses radiographically or succumbs to the disease, assessed up to 2 years
Overall response rate
Will be estimated by measuring the number of patients who achieve a complete response or partial response by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria on restaging computed tomography or magnetic resonance imaging scans =\< 6 months from PRRT completion, from the total number of patients who received the study treatment and possessed measurable disease post-surgical debulking. The number of patients who possessed measurable disease which did not meet RECIST 1.1 eligibility criteria post-surgical debulking will also be recorded.
Time frame: Up to 2 years
Overall survival
Will be estimated by the Kaplan-Meier method.
Time frame: From the start of PRRT to the date the patient progresses radiographically or succumbs to the disease, assessed up to 2 years
Incidence of adverse events
Toxicity will be estimated by documenting the grade 3/4 adverse events, according to Common Terminology Criteria for Adverse Events version 5.0, experienced by study patients.
Time frame: Up to 2 years
Gene mutations
Mutations in genes associated with radioresistance (defined from other malignancies) and other mutations in large resected neuroendocrine tumors will be recorded. Mutations will be described descriptively.
Time frame: Up to 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.