Phase II Non-Randomized Study Evaluating POSLUMA-PSMA PET Response After Oligo- Metastatic/Progressive-directed Treatment With Radiotherapy (PROMPT-R)

Inclusion

• Primary site of disease (Prostate +/- Seminal Vesicles) is controlled or will receive ablative intent treatment as a part of this treatment course.
• Eligible to receive ablative-intent radiation therapy (biologically effective dose \[BED\] \>100, α/β ratio:2) directed to all sites of metastatic disease.
• For the current treatment course, patient must not have received more than 3 months of neoadjuvant ADT prior to consent.
• Biopsy-confirmed diagnosis of castration-sensitive prostate adenocarcinoma, as defined by rising PSA in setting of T\>100
• Patients with a history or evidence of HIV infection (unless on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial).
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
• Patients with a history or evidence of hepatitis C virus (HCV) infection (unless treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load).
• Any contraindication to receiving flotufolastat F 18.
• Patients with history or evidence of chronic hepatitis B virus (HBV) infection (unless HBV viral load is undetectable on suppressive therapy).
• Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 30 days after the last dose of protocol therapy. \* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only).Exclusion CriteriPrior and concomitant therapies
• Clinical diagnosis of de novo oligometastatic or oligoprogressive disease, as defined by one the following:De novo oligometastatic: newly diagnosed prostate cancer AND ≤ five metastatic sites outside of the pelvis (Metastatic sites may not be brain or liver.) OR Hormone Sensitive Oligoprogressive: history of prior local therapy for prostate cancer AND ≤ five progressing metastatic sites outside of the pelvis (Metastatic sites may not be brain or liver.) AND Hormone sensitive defined as clinical progression in absence of castration (T\>100)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
• Baseline flotufolastat F18 PET imaging, if obtained as part of standard of care, is acceptable provided it was performed prior to the initiation of radiation therapy.
• Diagnosis of polyprogressive disease (History of metastatic prostate cancer with more than five progressive metastatic sites outside of the pelvis or metastatic sites in brain or liver).
• Diagnosis of polymetastatic (newly diagnosed prostate cancer and more than five metastatic sites outside of the pelvis or metastatic sites in brain or liver.)
• KPS ≥ 70 or ECOG 0-1 (Appendix A)
• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Clinically significant uncontrolled illness.
• Any patient planning to receive lifelong continuous or intermittent ADT
• Measurable disease by PERCIST v1.0
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
• Any contraindications to undergo PSMA-PET.

Exclusion

Exclusion criteria not yet provided.