A First-in-human Clinical Trial to Evaluate an Alpha-radiation Imaging Agent

A Phase 0 First-in-human Clinical Trial of [203Pb]VMT-α-NET SPECT/CT for Somatostatin Receptor Imaging of Neuroendocrine Tumors

This is a first in man study to determine if [203Pb]VMT-α-NET identifies neuroendocrine tumors with SPECT/CT. This is the first step to testing [212Pb]-based alpha radiation therapy in neuroendocrine therapy.

Study Overview

• Status: Enrolling by invitation
• Conditions: Neuroendocrine Tumor Grade 2; Neuroendocrine Tumor Grade 1
• Intervention / Treatment: Drug: [203Pb]VMT-α-NET; Device: SPECT/CT

Detailed Description

The goal of this work is to use [203Pb]VMT-α-NET as the imaging agent to create a specialized patient treatment plan using [212Pb]VMT-α-NET as a first-in-human therapy for treatment resistant or refractory neuroendocrine tumors of the foregut or midgut. The first step is to test the imaging agent [203Pb]VMT-α-NET. This requires a very small dose of the drug (microdose) which is then measured by a series of images (like CT scans) over 4 days. Blood samples are also drawn that that time. It is hoped the imaging will identify the tumors so that a therapy using [212Pb]VMT-α-NET can be created.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa

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 willingness to provide informed consent
• Stated willingness to comply with all study procedures and availability for duration of study
• Aged ≥ 18 years at the time of study drug administration
• Pathologically confirmed (histology or cytology) well-differentiated neuroendocrine tumor (WHO Grade 1 or 2) with primary location known or believed to be midgut or foregut
• At least 1 somatostatin receptor positive tumor site as demonstrated by PET/CT study utilizing an FDA approved PET agent within 12 months of consent
• ≥1 evaluable site of disease measuring ≥ 2.0 cm in any dimension on CT or MRI
• Adequate performance status (ECOG of 0 or 1; or KPS of ≥70).
• Not experiencing an uncontrolled intercurrent illness such as: infection requiring inpatient admission, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations, or any other condition that would limit compliance with study requirements as determined by study team members.

Exclusion Criteria:

• Individuals who are pregnant or breast feeding. A pregnancy test will be administered to individuals of child-bearing potential (per institutional policies) at screening. Individuals must agree to pregnancy tests prior to each administration of a radionuclidic agent for this study.
• Individuals of reproductive potential who decline to use effective contraception through the study (22 days equaling 10 half-lives).
• Lactating individuals who decline to withhold breastfeeding their child. As the effects of [203Pb]VMT-α-NET on the infant are unknown and relatively long half-life, women may not resume breast feeding for the current child.
• Therapeutic investigational drug within 4 weeks of C1D1
• Patients for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk.
• Subject's weight exceeds the limit of the imaging system.
• Long-acting somatostatin analogue treatment ≤ 20 days of C1D1
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to [90Y]DOTA-tyr3-Octreotide, Octreoscan®, or [68Ga]Octreotide.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [203Pb]VMT-α-NET SPECT/CT; injection of [203Pb]VMT-α-NET with serialized imaging and dosimetry measurements	Drug: [203Pb]VMT-α-NET; 3 to 5 miliCuries of [203]Pb administered intravenously 60 minutes before the start of the scans.; Device: SPECT/CT; Scans are administered over 3 days: 1 hour post injection, 4 to 8 hours post-injection, 24 to 30 hours post-injection, and 42 to 52 hours post-injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability of [203Pb]VMT-α-NET to identify neuroendocrine tumor lesions	percentage of lesions detected with [203Pb]VMT-α-NET compared to the gold standard of NetSPOT or Ga-68 DOTATOC.	Study days 1 through 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure radiation dose from [203Pb]VMT-α-NET dosimetrically	Determine the radiation absorbed dose to the organs and effective dose by pharmacokinetics through imaging and blood-measurements.	Study days 1 through 5
Single-time point survey	Evaluate the potential of feasibility of single-time point imaging to measure the renal radiation dose	Study days 1 through 5

Collaborators and Investigators

• Sponsor: Yusuf Menda
• Collaborators: National Cancer Institute (NCI); Holden Comprehensive Cancer Center; Perspective Therapeutics
• Investigators: Study Chair: Yusuf Menda, M.D., University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2022
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 30, 2021
• First Submitted That Met QC Criteria: October 30, 2021
• First Posted (Actual): November 8, 2021

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Alpha Particles; Pb-203 radioisotope; Single Photon Emission Computed Tomography Computed Tomography; SPECT CT Scan
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Neuroendocrine Tumors
• Other Study ID Numbers: 202006288; 5R01CA243014 (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 from those patient partners who agree to it. Data will be codified for the investigational team to provided additional details - as necessary - or confirm against source.
• IPD Sharing Time Frame: After study completion
• IPD Sharing Access Criteria: email the study chair; a non-disclosure and/or data usage agreement will most likely be required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes