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

Neuroendocrine Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03724409
• Other study ID #: 201805910
• Secondary ID: P50CA174521
• Status: Terminated
• Phase: Early Phase 1
• Start date: October 11, 2018
• Est. completion date: May 23, 2023

Study information

• Verified date: November 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: May 23, 2023
• Est. primary completion date: March 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuroendocrine Tumors

Intervention

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.

Locations

Country	Name	City	State
United States	The Holden Comprehensive Cancer Center	Iowa City	Iowa

Sponsors (4)

Lead Sponsor	Collaborator
Sandeep Laroia	Holden Comprehensive Cancer Center, National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	90Y-DOTATOC distribution	Determine the distribution of 90Y-DOTATOC using post-treatment imaging	48h post-infusion