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

Phase 1
Recruiting
Conditions
Gastroenteropancreatic Neuroendocrine Tumor
Interventions
Procedure: Computed Tomography (CT)
Procedure: Magnetic Resonance Imaging (MRI)
Procedure: PET/CT
Registration Number
NCT04609592
Lead Sponsor
Stanford University
Brief Summary

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

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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
10
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
LutatheraLutathera2 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
LutatheraGallium 68 Dotatate2 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
LutatheraPET/CT2 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
LutatheraMagnetic Resonance Imaging (MRI)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
LutatheraComputed Tomography (CT)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
Primary Outcome Measures
NameTimeMethod
Measure Complication free Surgery6 months

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)

Secondary Outcome Measures
NameTimeMethod
Recurrence free Survival (RFS)1 year

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.

Response Rate (RR)16 weeks

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

Overall Survival (OS)1 year

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.

Trial Locations

Locations (1)

Stanford Cancer Institute Palo Alto

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Stanford, California, United States

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