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

• ClinicalTrials.gov Identifier: NCT03724409
• Recruitment Status: Recruiting
• First Posted: October 30, 2018
• Last Update Posted: September 6, 2019
• Sponsor: Sandeep Laroia
• Collaborators: National Institutes of Health (NIH); Holden Comprehensive Cancer Center; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Sandeep Laroia, University of Iowa

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumors	Drug: [90]Y-DOTATOC	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: This is a sequential early phase 1 study using Storer's phase 1 design B.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Selective Intra-arterial Injection of Peptide Receptor Radionuclide Therapy (PRRT) in Neuroendocrine Tumor Patients With Liver Metastases
• Actual Study Start Date: October 11, 2018
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in liver enzymes [ Time Frame: Through 6 weeks after treatment ]
   Evaluate liver toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for liver enzymes
2. Change in platelet counts [ Time Frame: Through 6 weeks after treatment ]
   Evaluate bone marrow toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for platelet count
3. Change in absolute neutrophil count [ Time Frame: Through 6 weeks after treatment ]
   Evaluate bone marrow toxicity using using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for absolute neutrophil count

Secondary Outcome Measures :

1. 90Y-DOTATOC distribution [ Time Frame: 48h post-infusion ]
   Determine the distribution of 90Y-DOTATOC using post-treatment imaging

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Sandeep Laroia, MD; (319) 356-3859; sandeep-laroia@uiowa.edu

Contact: Yusuf Menda, MD; (319) 356-3214; yusuf-menda@uiowa.edu

Locations

United States, Iowa

The Holden Comprehensive Cancer Center; Recruiting

Iowa City, Iowa, United States, 52242

Contact: Kristin Gaimari-Varner, RN, BSN 319-384-5489 kristin-gaimari-varner@uiowa.edu

Contact: Veronica Howsare (319) 384-6469 veronica-howsare@uiowa.edu

Sponsors and Collaborators

Sandeep Laroia

National Institutes of Health (NIH)

Holden Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

• Study Chair: M. S O'Dorisio, MD, PhD; University of Iowa
• Principal Investigator: Sandeep Laroia, MD; University of Iowa

More Information

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. Review.

• Responsible Party: Sandeep Laroia, Associate Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT03724409 History of Changes
• Other Study ID Numbers: 201805910; P50CA174521 ( U.S. NIH Grant/Contract )
• First Posted: October 30, 2018
• Last Update Posted: September 6, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Considered upon request.
• Access Criteria: Contact study PI regarding data sharing. A non-disclosure agreement may be required between institutions dependent upon the data requested.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sandeep Laroia, University of Iowa:

PRRT; Radionuclide; DOTATOC; intra-arterial; peptide receptor radiotherapy

Additional relevant MeSH terms:

Neuroendocrine Tumors; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Octreotide; Edotreotide; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Radiopharmaceuticals; Molecular Mechanisms of Pharmacological Action