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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Neuroendocrine Tumor Grade 2, Neuroendocrine Tumor Grade 1

Intervention / Treatment
-----------------
* Drug: [203Pb]VMT-α-NET
* Device: SPECT/CT


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [203Pb]VMT-α-NET SPECT/CT<br>injection of [203Pb]VMT-α-NET with serialized imaging and dosimetry measurements | Drug: [203Pb]VMT-α-NET<br>* 3 to 5 miliCuries of [203]Pb administered intravenously 60 minutes before the start of the scans.<br>Device: SPECT/CT<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alpha Particles, Pb-203 radioisotope, Single Photon Emission Computed Tomography Computed Tomography, SPECT CT Scan