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

NCT ID: NCT03724409

Last Updated: 2023-11-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-11
• Study Completion Date: 2023-05-23

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.

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.

Conditions

Neuroendocrine Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

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

Group Type: EXPERIMENTAL

[90]Y-DOTATOC

Intervention Type: 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.

Cohort 2

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

Group Type: EXPERIMENTAL

[90]Y-DOTATOC

Intervention Type: 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.

Cohort 3

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

Group Type: EXPERIMENTAL

[90]Y-DOTATOC

Intervention Type: 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.

Cohort 4

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

Group Type: EXPERIMENTAL

[90]Y-DOTATOC

Intervention Type: 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.

Cohort 5

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

Group Type: EXPERIMENTAL

[90]Y-DOTATOC

Intervention Type: 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.

Cohort 6

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

Group Type: EXPERIMENTAL

[90]Y-DOTATOC

Intervention Type: 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.

Interventions

[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.

Intervention Type: DRUG

Other Intervention Names

90Y-DOTATOC; 90Y-DOTA-Phe1-tyr3-Octreotide; [90]Yttrium-DOTATOC

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Holden Comprehensive Cancer Center

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sandeep Laroia

OTHER

Sponsor Role: lead

Responsible Party

Sandeep Laroia

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

M. S O'Dorisio, MD, PhD

Role: STUDY_CHAIR

University of Iowa

Sandeep Laroia, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

The Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 25186181 (View on PubMed)

Other Identifiers

P50CA174521

Identifier Type: NIH

Identifier Source: secondary_id

View Link

201805910

Identifier Type: -

Identifier Source: org_study_id