a first-in-human clinical trial to evaluate an alpha-radiation imaging agent

Conditions: Neuroendocrine Tumor Grade 2; Neuroendocrine Tumor Grade 1

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.

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.

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.

Keywords: alpha particles pb-203 radioisotope single photon emission computed tomography computed tomography spect ct scan