Exploratory PK and Imaging Study of PSMA-Targeted Trillium Compounds and PTI-122 in Metastatic Prostate Cancer

Study Overview
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Brief Summary
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Exploratory study in adult males with metastatic prostate cancer intended to characterize the pharmacokinetics and biodistribution of PSMA-Targeted [In-111]-Labeled Trillium Compounds with and without the cytoprotective agent PTI-122. Up to 36 eligible subjects will be enrolled. Additional subjects may be enrolled if there is insufficient data for evaluation, for example if the original study subjects do not complete required imaging studies for reasons unrelated to adverse events. Up to four PSMA-Targeted [In-111]-Labeled Trillium Compounds will be evaluated. Each compound will be evaluated first without the cytoprotective agent, PTI-122, then the [In-111]-labeled Trillium Compound may be co-administered with PTI-122.

Official Title
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A Phase 0 Study of the Pharmacokinetics and Biodistribution of PSMA-Targeted [In-111]-Labeled Trillium Compounds With and Without PTI-122 in Patients With Metastatic Prostate Cancer to Inform Future Phase 1 Dosing With [Ac-225]-Trillium-PSMA Radionuclide Therapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: PSMA-Targeted [In-111]-Labeled Trillium Compound
* Drug: PTI-122


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males with metastatic prostate cancer ECOG performance score 0-2 Stable androgen deprivation or other hormone therapy (30 days) or therapy planned but not yet initiated PSMA PET scan between 3 and 28 days prior to radiotracer injection with at least 2 PSMA positive lesions and either: One soft tissue lesion measuring ≥ 15 mm in the longest diameter with SUVmax lesion ≥ SUVmean normal liver, OR Two bone lesions measuring ≥ 15 mm in the longest diameter with SUVmax lesion ≥ 2 x SUVmax normal liver Able to understand and adhere to study requirements, and voluntarily give informed consent Exclusion Criteria: No other malignancy undergoing treatment No PSMA-targeted therapy ongoing Inability or unwillingness to undergo SPECT/CT imaging Serum creatinine > 1.5 mg/dL or creatinine clearance ≤50 mL/min by Cockcroft-Gault estimation Concurrent participation in the active treatment phase of another clinical trial of investigational medicinal product(s) Significant intercurrent illness, treatment-related toxicity, or psychiatric illness/social situation that could place the subject at undue risk during study participation, significantly alter study outcomes, or affect subject compliance with study requirements for dosing and evaluation, as determined by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Each Trillium Compound will first be evaluated alone, then with single doses (5, 10, 15 mg) of the cytoprotective agent, PTI-122. Trillium Compound with two doses of PTI-122 at the preferred dose level may be studied if indicated.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trillium Compound Alone<br>Single dose of PSMA-Targeted [In-111]-Labeled Trillium Compound | Drug: PSMA-Targeted [In-111]-Labeled Trillium Compound<br>* Radiotracer<br>|
| Experimental: Trillium Compound + Single Dose PTI-122<br>Single dose of PSMA-Targeted [In-111]-Labeled Trillium Compound plus single dose of PTI-122 at 5, 10 or 15 mg | Drug: PSMA-Targeted [In-111]-Labeled Trillium Compound<br>* Radiotracer<br>Drug: PTI-122<br>* Cytoprotective agent<br>|
| Experimental: Trillium Compound + Multiple Dose PTI-122<br>Single dose of PSMA-Targeted [In-111]-Labeled Trillium Compound plus two doses of PTI-122 at the preferred dose level | Drug: PSMA-Targeted [In-111]-Labeled Trillium Compound<br>* Radiotracer<br>Drug: PTI-122<br>* Cytoprotective agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of radiotracer absorbed by tumor | Tumor uptake measured on imaging | Over 168 hours post-injection | 
| Amount of radioactivity in blood | Radioactivity measured pre- and post-radiotracer injection | Over 168 hours post-injection | 
| Amount of radiotracer absorbed by organs | Organ uptake measured on imaging | Over 168 hours post-injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of PTI-122 in blood | PTI-122 measured pre- and post-dose | Over 168 hours post-injection | 
| Incidence of adverse events | Occurrence of adverse events during the study | Over 168 hours post-injection |