Selective Intra-arterial Injection of PRRT in Neuroendocrine Tumor Patients With Liver Metastases

Selective Intra-arterial Injection of Peptide Receptor Radionuclide Therapy (PRRT) in Neuroendocrine Tumor Patients With Liver Metastases

This is a safety study to determine the phase 1 starting dose of [90]Yttrium-DOTATOC when it is administered intravenously for patients with neuroendocrine tumors that have spread to the liver.

Study Overview

• Status: Terminated
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: [90]Y-DOTATOC

Detailed Description

[90]Yttrium-DOTATOC is a radioactive drug used for peptide receptor radionuclide therapy (PRRT). In other studies, 90Y-DOTATOC has been administered through a vein (IV) to target somatostatin receptor positive tumor tissue. The DOTATOC identifies the tumor through the somatostatin receptor and links to it, attaching the radioactive molecule 90Yttrium to the malignant cell.

This study expands the initial work to examine if administering the drug 90Y-DOTATOC directly to the liver is safe for patients with neuroendocrine tumors whose disease has spread to their tumor. We don't know how of the 90Y-DOTATOC is safe to administer. We want to learn what the maximum safe dose is and what the side effects are related to that dose.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The Holden Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ability to understand and the willingness to provide informed consent
• Pathologically well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2).
• Primary tumor location should be known or believed to be midgut.
• At least one tumor in the liver that is positive with [68]Ga-DOTATATE (NETSPOT). Imaging must be performed within the past 6 months.
• Liver lesions not amendable to other therapies (surgery, ablation) and have progressed after treatment with octreotide/lanreotide and/or other treatments. (everolimus, sunitinib).
• Karnofsky performance status of at least 70
• Absolute neutrophil count of at least 1,000 cells/mm3
• Platelet count of at least 90,000 cells / mm3
• Total bilirubin ≤ 2 x the upper limit of normal when adjusted for age
• AST and ALT ≤ 5 x the upper limit of normal when adjusted for age
• Serum creatinine ≤ 1.2 mg/dl; if serum creatinine is >1.2 mg/dl nuclear GFR will used for potentially eligible participants.
• Agrees to contraception.

Exclusion criteria:

• Liver tumor involvement greater than 70% by cross sectional imaging
• Extra-hepatic visceral and osseous metastases
• Concomitant therapy for tumor (except for somatostatin analogs or bisphosphonates)
• Previous PRRT or other liver directed therapy within 12 months of consent
• Women who are pregnant, breast feeding or breast pumping.
• Another concurrent malignancy on active therapy
• Previous external-beam radiation therapy to a kidney (including scatter dose)
• Therapeutic investigational drug within 4 weeks of therapy.
• Subjects for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk.
• Sandostatin LAR injection within 4 weeks or lanreotide injection within 8 weeks of proposed therapy.
• Inability to lie down supine for study procedure.
• Reaction to IV contrast used for the angiogram.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring hospitalization, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Subject will be administered 2.96 gigabecquerels of [90]Y-DOTATOC intra-aterially to the liver	Drug: [90]Y-DOTATOC; Intra-arterial infusion to the liver of [90]Y-DOTATOC. The administered dose is determined by cohort and is dependent upon the results of the previous cohort.; Other Names: 90Y-DOTATOC; 90Y-DOTA-Phe1-tyr3-Octreotide; [90]Yttrium-DOTATOC
Experimental: Cohort 2; Subject will be administered 3.33 gigabecquerels of [90]Y-DOTATOC intra-aterially to the liver	Drug: [90]Y-DOTATOC; Intra-arterial infusion to the liver of [90]Y-DOTATOC. The administered dose is determined by cohort and is dependent upon the results of the previous cohort.; Other Names: 90Y-DOTATOC; 90Y-DOTA-Phe1-tyr3-Octreotide; [90]Yttrium-DOTATOC
Experimental: Cohort 3; Subject will be administered 3.7 gigabecquerels of [90]Y-DOTATOC intra-aterially to the liver	Drug: [90]Y-DOTATOC; Intra-arterial infusion to the liver of [90]Y-DOTATOC. The administered dose is determined by cohort and is dependent upon the results of the previous cohort.; Other Names: 90Y-DOTATOC; 90Y-DOTA-Phe1-tyr3-Octreotide; [90]Yttrium-DOTATOC
Experimental: Cohort 4; Subject will be administered 4.17 gigabecquerels of [90]Y-DOTATOC intra-aterially to the liver	Drug: [90]Y-DOTATOC; Intra-arterial infusion to the liver of [90]Y-DOTATOC. The administered dose is determined by cohort and is dependent upon the results of the previous cohort.; Other Names: 90Y-DOTATOC; 90Y-DOTA-Phe1-tyr3-Octreotide; [90]Yttrium-DOTATOC
Experimental: Cohort 5; Subject will be administered 4.44 gigabecquerels of [90]Y-DOTATOC intra-aterially to the liver	Drug: [90]Y-DOTATOC; Intra-arterial infusion to the liver of [90]Y-DOTATOC. The administered dose is determined by cohort and is dependent upon the results of the previous cohort.; Other Names: 90Y-DOTATOC; 90Y-DOTA-Phe1-tyr3-Octreotide; [90]Yttrium-DOTATOC
Experimental: Cohort 6; Subject will be administered 5.18 gigabecquerels of [90]Y-DOTATOC intra-aterially to the liver	Drug: [90]Y-DOTATOC; Intra-arterial infusion to the liver of [90]Y-DOTATOC. The administered dose is determined by cohort and is dependent upon the results of the previous cohort.; Other Names: 90Y-DOTATOC; 90Y-DOTA-Phe1-tyr3-Octreotide; [90]Yttrium-DOTATOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver enzymes	Evaluate liver toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for liver enzymes	Through 6 weeks after treatment
Change in platelet counts	Evaluate bone marrow toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for platelet count	Through 6 weeks after treatment
Change in absolute neutrophil count	Evaluate bone marrow toxicity using using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for absolute neutrophil count	Through 6 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90Y-DOTATOC distribution	Determine the distribution of 90Y-DOTATOC using post-treatment imaging	48h post-infusion

Collaborators and Investigators

• Sponsor: Sandeep Laroia
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH); Holden Comprehensive Cancer Center
• Investigators: Study Chair: M. S O'Dorisio, MD, PhD, University of Iowa; Principal Investigator: Sandeep Laroia, MD, University of Iowa

Publications and helpful links

General Publications

• Kennedy A, Bester L, Salem R, Sharma RA, Parks RW, Ruszniewski P; NET-Liver-Metastases Consensus Conference. Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference. HPB (Oxford). 2015 Jan;17(1):29-37. doi: 10.1111/hpb.12326. Epub 2014 Sep 4.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2018
• Primary Completion (Actual): March 21, 2021
• Study Completion (Actual): May 23, 2023

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (Actual): October 30, 2018

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: PRRT; Radionuclide; DOTATOC; intra-arterial; peptide receptor radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Radiopharmaceuticals; Octreotide; Edotreotide
• Other Study ID Numbers: 201805910; P50CA174521 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared as per approved IRB application and the subject's opt-in preferences. Data will not be provided from subjects who decline data sharing.
• IPD Sharing Time Frame: Considered upon request.
• IPD Sharing Access Criteria: Contact study PI regarding data sharing. A non-disclosure agreement may be required between institutions dependent upon the data requested.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No