Study of PRRT in Metastatic, World Health Organization (WHO) Grade 1 or 2, SSTR Positive, GEP-NET Who Are Candidates for Cytoreductive Surgery

Study Overview
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Brief Summary
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The purpose of this study is to learn about the feasibility and safety of using Peptide Receptor Radionuclide Therapy (PRRT) before and after surgical removal of a tumor. PRRT treatment is based on the administration of a radioactive product, 177-Lu DOTA-0-Tyr3-Octreotate (Lutathera®) and its use before and after surgery is thought to increase the overall survival benefit for patients with SSTR-positive gastroenteropancreatic neuroendocrine tumors GEP-NETs.

Detailed Description
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Primary Objective(s) To assess feasibility and safety of combination of perioperative 177Lu Dotatate and cytoreductive surgery in metastatic GEP NETs Secondary Objective(s) To assess response rate (RR) after 2 cycles 177Lu Dotatate To assess recurrence free survival (RFS) of the overall treatment strategy To assess overall survival (OS) of the overall treatment strategy

Official Title
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Pilot Phase 1 Study of Perioperative Peptide Receptor Radionuclide Therapy (PRRT) in Metastatic, WHO Grade 1 or 2, SSTR Positive, Gastroenteropancreatic Neuroendocrine Tumors Who Are Candidates for Cytoreductive Surgery

Conditions
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Gastroenteropancreatic Neuroendocrine Tumor

Intervention / Treatment
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* Drug: Lutathera
* Drug: Gallium 68 Dotatate
* Procedure: Computed Tomography (CT)
* Procedure: Magnetic Resonance Imaging (MRI)
* Procedure: PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic gastroenteropancreatic NET with lymph nodes or liver metastases only. WHO Grade 1 or 2, Ki 67 ≤ 20% (to be confirmed at Stanford) Must be a candidate for cytoreductive surgery with the goal of R1 resection as determined by a multidisciplinary tumor board discussion Measurable disease as determined by RECIST v1.1 Confirmed presence of somatostatin receptors on all target lesions as determined by 68Ga DOTA TATE PET scan Patients ≥ 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1 Appropriate hematologic, liver and kidney function Patients on octreotide long-acting release (LAR) at a fixed dose of 20 mg or 30 mg at 3 to 4 weeks intervals for at least 12 weeks prior to enrollment in the study Exclusion Criteria: Prior 177Lu Dotatate treatment Any surgery or radiofrequency ablation within 12 weeks prior to enrollment in the study; or prior radioembolization; chemoembolization; or external beam radiation therapy (EBRT) to > 25% of bone marrow, at any time Any chemotherapy or targeted therapy (including everolimus and sunitinib) within 4 weeks prior to enrollment in the study Known brain metastases Known bone or peritoneal metastases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lutathera<br>2 cycles of 177Lu Dotatate, followed by cytoreductive surgery, followed by additional 177Lu Dotatate (up to 2 cycles) for residual disease as determined by 68Ga DOTA TATE PET/CT | Drug: Lutathera<br>* 4 administrations of 7.4 gigabecquerel (GBq) (200 mCi) 177Lu Dotatate +/ 10% at the date and time of infusion, accumulative dose of 29.6 GBq (800 mCi). T<br>* Other names: 177 Lu-DOTA-octreotate;Drug: Gallium 68 Dotatate<br>* Standard of care, 2 Megabecquerel (MBq)/kg (0.054 mCi/kg) up to 200 MBq (5.4 mCi)<br>* Other names: Gallium-68 DOTA-DPhe1, Tyr3-octreotate;Procedure: Computed Tomography (CT)<br>* Medical Imaging<br>* Other names: CT Scan;Procedure: Magnetic Resonance Imaging (MRI)<br>* Medical Imaging<br>Procedure: PET/CT<br>* Medical Imaging<br>* Other names: Positron Emission Tomography (PET);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Complication free Surgery | The feasibility of perioperative 177Lu Dotatate as part of the therapeutic regimen to treat metastatic neuroendocrine tumors (NETs) will be assessed on the basis of number and proportion of participants who undergo 2 cycles of complication free 177Lu Dotatate therapy followed by cytoreductive surgery without complications, expressed as a number without dispersion. Complications are defined as follows. Radiation fibrosis Hepatic fibrosis by histologic diagnosis Hepatic insufficiency Bowel anastamotic leak (if bowel surgery) Distal pancreatic leak (if pancreas surgery) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (RR) | Response Rate (RR), as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, will be determined after 2 pre operative cycles of 177Lu Dotatate. RR will be assessed as the sum of complete response (CR) and partial response (PR), and expressed as a number without dispersion. RECIST criteria are: CR = Disappearance of all target lesions PR = ≥ 30% decrease in the sum of the longest diameter of target lesions Response Rate (RR) = CR + PR Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) Stable disease (SD) = Small changes that do not meet any of the above criteria | 16 weeks | 
| Recurrence free Survival (RFS) | Recurrence free Survival (RFS) is defined as the number and proportion of participants that remain alive from the start of treatment without relapse or recurrence of disease, expressed as a number without dispersion. | 1 year | 
| Overall Survival (OS) | Overall survival (OS) is defined as the number and proportion of participants that remain alive from the start of treatment, expressed as a number without dispersion. | 1 year |