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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastroenteropancreatic Neuroendocrine Tumor
• Intervention / Treatment: Drug: Lutathera; Drug: Gallium 68 Dotatate; Procedure: Computed Tomography (CT); Procedure: Magnetic Resonance Imaging (MRI); Procedure: PET/CT

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gino Pinedo; Phone Number: 650-725-8474; Email: gpineda@stanford.edu
• Study Contact Backup: Name: gitrialeligibility@stanford.edu gitrialeligibility@stanford.edu; Phone Number: (650) 498-7757; Email: gitrialeligibility@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 95304
      • Recruiting
      • Stanford Cancer Institute Palo Alto
      • Principal Investigator: Brendan C Visser, MD
      • Contact: Email: gitrialeligibility@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Metastatic gastroenteropancreatic NET with lymph nodes or liver metastases only.
2. WHO Grade 1 or 2, Ki 67 ≤ 20% (to be confirmed at Stanford)
3. Must be a candidate for cytoreductive surgery with the goal of R1 resection as determined by a multidisciplinary tumor board discussion
4. Measurable disease as determined by RECIST v1.1
5. Confirmed presence of somatostatin receptors on all target lesions as determined by 68Ga DOTA TATE PET scan
6. Patients ≥ 18 years of age.
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
8. Appropriate hematologic, liver and kidney function
9. 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:

1. Prior 177Lu Dotatate treatment
2. 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
3. Any chemotherapy or targeted therapy (including everolimus and sunitinib) within 4 weeks prior to enrollment in the study
4. Known brain metastases
5. Known bone or peritoneal metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lutathera; 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; 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; Other Names: lutetium Lu 177 dotatate; (Lu 177)-N-[(4,7,10-Tricarboxymethyl-1,4,7,10- tetraazacyclododec-1-yl) acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-Lcysteinyl-L-threonine-cyclic (2-7) disulfide.; 177 Lu-DOTA-octreotate; Drug: Gallium 68 Dotatate; Standard of care, 2 Megabecquerel (MBq)/kg (0.054 mCi/kg) up to 200 MBq (5.4 mCi); Other Names: Gallium-68 DOTA-DPhe1, Tyr3-octreotate; Procedure: Computed Tomography (CT); Medical Imaging; Other Names: CT Scan; Procedure: Magnetic Resonance Imaging (MRI); Medical Imaging; Procedure: PET/CT; Medical Imaging; Other Names: Positron Emission Tomography (PET)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Brendan C Visser, MD, Stanford Universiy

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Estimated): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Intestinal Diseases; Pancreatic Diseases; Stomach Neoplasms; Pancreatic Neoplasms; Neuroendocrine Tumors; Intestinal Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Lutetium Lu 177 dotatate
• Other Study ID Numbers: IRB-52341; NET0030 (Other Identifier: OnCore); NCI-2021-03448 (Registry Identifier: CTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No