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.

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.

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.