PSMA PET Response Guided SabR in High Risk Pca

Study Overview
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Brief Summary
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Sequential cohort evaluation of ideal timing of imaging and treatment spacing to discern maximal PSMA (Prostate specific membrane antigen) PET (Positron Emission Tomography) response (PSMA-11 68Ga, Illucix) for adaptation of dominant intra-prostatic lesion tumor boost dose

Official Title
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Phase IB Study of Personalized Ultrahypofractionated Stereotactic Ablative Radiotherapy of High Risk PROstate Cancer Guided by PET PSMA (68Ga PMSA-11; Ilucix) Response (PULSAR ProPhet)

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: 68-Ga PSMA11


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Pathologically confirmed adenocarcinoma of the prostate (within 180 days of registration) of high risk by national comprehensive cancer network (NCCN) criteria as determined by >=cT3a stage (AJCC 8th edition) OR PSA>20ng/mL OR ISUP Grade Group 4-5 (Gleason Grade 8-10). Age ≥ 18 years. Planned for definitive intent stereotactic ablative radiotherapy (SabR) with integrated dose boost to intra-prostatic tumor and androgen deprivation therapy (ADT) with baseline AUA IPSS <=18 and prostate size <=100cc Staging 68Ga PMSA-11 PET -CT or -MRI performed within 90 days of registration and before initiation of anti-androgen or androgen deprivation therapy and demonstrating no evidence of distant metastases by (PMSA avid or non-avid nodes <=1.5cm short axis allowed). Conventional imaging (CT, bone scan, MRI) may also be used in addition to PMSA-PET, and definitive findings of distant extra-pelvic metastases on these scans are not allowed for enrollment. Staging 68Ga PSMA-11 PET -CT or -MRI demonstrating a PSMA-avid primary intra-prostatic target lesion amenable at investigator discretion to dose boost All men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of standard of care SabR and for a period of time of 6 months thereafter as per standard guidelines. Should a man's partner become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: Prior curative intent local therapy (e.g. prostatectomy, radiotherapy, focal ablative therapy) for prostate cancer is not allowed, with following exceptions regarding androgen deprivation therapy (ADT)/anti-androgen therapy (AAT): Prior androgen deprivation therapy (ADT) allowed if <3 month total duration and stopped >=3 months prior to registration with demonstration of non-castrate testosterone recovery (>50ng/dL) and meeting all other inclusion criteria. Ongoing androgen deprivation therapy (ADT) is allowed if <=60 days total duration AND meeting following criteria: If GnRH agonist used (e.g. leuprolide), bicalutamide must have been used for at least 30 days +/-14 days from start of GnRH agonist. All other inclusion criteria. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study. History of allergic reactions to PMSA-11 68Ga imaging agent. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements. Prior pelvic radiotherapy other than cutaneous/superficial treatments.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAbR Every other day<br>SAbR given 2-3/week, at least every other day in spacing with long-term ADT (neoadjuvant ADT x 3months required) with experimental Illucix (PSMA-11 68Ga) PET before and during SAbR (between fraction 3 and 4) to assess and adapt to dominant intra-prostatic lesion boost dose. | Drug: 68-Ga PSMA11<br>* Will be injected/assessed in line with its FDA label.<br>* Other names: Illucix, Telix;|
| Experimental: PULSAR every week<br>SAbR given 1/week, with long-term ADT (neoadjuvant ADT x 3months required) with experimental Illucix (PSMA-11 68Ga) PET before and during SAbR (between fraction 3 and 4) to assess and adapt to dominant intra-prostatic lesion boost dose. | Drug: 68-Ga PSMA11<br>* Will be injected/assessed in line with its FDA label.<br>* Other names: Illucix, Telix;|
| Experimental: PULSAR every 2 weeks<br>SAbR given every 2 weeks, with long-term ADT (neoadjuvant ADT x 3months required) with experimental Illucix (PSMA-11 68Ga) PET before and during SAbR (between fraction 3 and 4) to assess and adapt to dominant intra-prostatic lesion boost dose. | Drug: 68-Ga PSMA11<br>* Will be injected/assessed in line with its FDA label.<br>* Other names: Illucix, Telix;|
| Experimental: PULSAR every 3 weeks<br>SAbR given every 3 weeks, with long-term ADT (neoadjuvant ADT x 3months required) with experimental Illucix (PSMA-11 68Ga) PET before and during SAbR (between fraction 3 and 4) to assess and adapt to dominant intra-prostatic lesion boost dose. | Drug: 68-Ga PSMA11<br>* Will be injected/assessed in line with its FDA label.<br>* Other names: Illucix, Telix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Target Intra-Prostatic Lesion(s) | This study primarily evaluates volume reduction of initial target PSMA-avid dominant intra-prostatic disease after neoadjuvant ADT and during SAbR in differing spacing regimens of SAbR. Metrics include percent reduction in volume at 3 months of therapy vs initial disease extent of intra-prostatic dominant lesion as identified by PSMA PET. | Through end of neoadjuvant ADT at 3 months |