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

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Primary Purpose

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Lutathera

Gallium 68 Dotatate

Computed Tomography (CT)

Magnetic Resonance Imaging (MRI)

PET/CT

About this trial

This is an interventional treatment trial for Gastroenteropancreatic Neuroendocrine Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford Cancer Institute Palo AltoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lutathera

Arm Description

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

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.

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.

Full Information

NCT ID

NCT04609592

First Posted

October 23, 2020

Last Updated

July 14, 2023

Sponsor

Stanford University

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04609592

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 17, 2021 (Actual)

Primary Completion Date

March 2024 (Anticipated)

Study Completion Date

September 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Stanford University

Collaborators

Novartis Pharmaceuticals

4. Oversight

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

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastroenteropancreatic Neuroendocrine Tumor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Lutathera

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Lutathera

Other Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Gallium 68 Dotatate

Other Intervention Name(s)

Gallium-68 DOTA-DPhe1, Tyr3-octreotate

Intervention Description

Standard of care, 2 Megabecquerel (MBq)/kg (0.054 mCi/kg) up to 200 MBq (5.4 mCi)

Intervention Type

Procedure

Intervention Name(s)

Computed Tomography (CT)

Other Intervention Name(s)

CT Scan

Intervention Description

Medical Imaging

Intervention Type

Procedure

Intervention Name(s)

Magnetic Resonance Imaging (MRI)

Intervention Description

Medical Imaging

Intervention Type

Procedure

Intervention Name(s)

PET/CT

Other Intervention Name(s)

Positron Emission Tomography (PET)

Intervention Description

Medical Imaging

Primary Outcome Measure Information:

Title

Measure Complication free Surgery

Description

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)

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Response Rate (RR)

Description

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

Time Frame

16 weeks

Title

Recurrence free Survival (RFS)

Description

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.

Time Frame

1 year

Title

Overall Survival (OS)

Description

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.

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Gino Pinedo

Phone

650-725-8474

Email

gpineda@stanford.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Brendan C Visser, MD

Organizational Affiliation

Stanford Universiy

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford Cancer Institute Palo Alto

City

Stanford

State/Province

California

ZIP/Postal Code

95304

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gino Pineda

Phone

650-725-8474

Email

gpineda@stanford.edu

First Name & Middle Initial & Last Name & Degree

Brendan C Visser, MD

12. IPD Sharing Statement

Plan to Share IPD

No

Gastroenteropancreatic Neuroendocrine Tumor

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial