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

NCT03724409 | Terminated Early Phase 1 DMC FDA Drug

• 2 other identifiers: 201805910P50CA174521
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuroendocrine Tumors

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• 90Y-DOTATOC distribution

  48h post-infusion

Study Arms (6)

Cohort 1

EXPERIMENTAL

Subject will be administered 2.96 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver

Drug: [90]Y-DOTATOC

Cohort 2

EXPERIMENTAL

Subject will be administered 3.33 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver

Drug: [90]Y-DOTATOC

Cohort 3

EXPERIMENTAL

Subject will be administered 3.7 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver

Drug: [90]Y-DOTATOC

Cohort 4

EXPERIMENTAL

Subject will be administered 4.17 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver

Drug: [90]Y-DOTATOC

Cohort 5

EXPERIMENTAL

Subject will be administered 4.44 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver

Drug: [90]Y-DOTATOC

Cohort 6

EXPERIMENTAL

Subject will be administered 5.18 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver

Drug: [90]Y-DOTATOC

Interventions

[90]Y-DOTATOC DRUG

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.

Also known as: 90Y-DOTATOC, 90Y-DOTA-Phe1-tyr3-Octreotide, [90]Yttrium-DOTATOC

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sandeep Laroia: lead
• National Institutes of Health (NIH): collaborator
• Holden Comprehensive Cancer Center: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

The Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Related Publications (1)

• 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.

  PMID: 25186181 BACKGROUND

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

90Y-octreotide, DOTA-Tyr(3)-

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• M. S O'Dorisio, MD, PhD

  University of Iowa

  STUDY CHAIR

• Sandeep Laroia, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a sequential early phase 1 study using Storer's phase 1 design B.

Study Record Dates

• First Submitted: October 25, 2018
• First Posted: October 30, 2018
• Study Start: October 11, 2018
• Primary Completion: March 21, 2021
• Study Completion: May 23, 2023
• Last Updated: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (1)