PSMA-PET and ctDNA monitoring after targeted radiotherapy for oligometastatic prostate cancer (PROMPT-R)

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

This will see if PSMA-PET scans and blood ctDNA can detect early progression and track response after ablative radiotherapy in men with oligometastatic or oligoprogressive, hormone-sensitive prostate cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: City of Hope Medical Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Duarte, California)
• Trial ID: NCT07210086 on ClinicalTrials.gov

What this trial studies

This Phase II non-randomized study uses serial PSMA-PET imaging and circulating tumor DNA (ctDNA) measurements to follow patients with de novo oligometastatic or hormone-sensitive oligoprogressive prostate cancer who receive ablative-intent radiotherapy to metastatic sites. Investigators will record how often PSMA-PET shows progression before PSA rises and will score lesion-by-lesion PET responses at 6 and 12 months. The study will correlate PET responses with PSA kinetics, later clinical or imaging progression, and changes in ctDNA after treatment. Participants may be on androgen-deprivation therapy or androgen receptor signaling inhibitors as clinically indicated, and all must be eligible for high-dose local radiotherapy to metastatic lesions.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with biopsy-confirmed, castration-sensitive prostate adenocarcinoma, KPS ≥70 or ECOG 0-1, clinical de novo oligometastatic or oligoprogressive disease with ≤5 metastatic sites outside the pelvis (no brain or liver mets), measurable disease by PERCIST, and eligible for ablative-intent radiotherapy (BED >100).

Not a fit: Patients with widespread disease (>5 metastatic sites), brain or liver metastases, castration-resistant disease, poor performance status, or who are unable/unwilling to undergo serial PSMA-PET imaging and ablative radiotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could enable earlier detection of progression and better personalize when to give systemic therapy or additional metastasis-directed treatments.

How similar studies have performed: PSMA-PET–guided metastasis-directed radiotherapy has shown promise in prior oligometastatic prostate studies, but combining serial PSMA-PET with ctDNA monitoring to guide response and detect early progression is relatively novel and less established.

Eligibility criteria

Inclusion Criteria:

* Documented informed consent of the participant or legally authorized representative.
* Age: ≥ 18 years
* KPS ≥ 70 or ECOG 0-1 (Appendix A)
* Biopsy-confirmed diagnosis of castration-sensitive prostate adenocarcinoma, as defined by rising PSA in setting of T\>100
* 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)

* Measurable disease by PERCIST v1.0
* Eligible to receive ablative-intent radiation therapy (biologically effective dose \[BED\] \>100, α/β ratio:2) directed to all sites of metastatic disease.
* Primary site of disease (Prostate +/- Seminal Vesicles) is controlled or will receive ablative intent treatment as a part of this treatment course.
* 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.
* 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

* Any patient planning to receive lifelong continuous or intermittent ADT
* For the current treatment course, patient must not have received more than 3 months of neoadjuvant ADT prior to consent.
* Any contraindication to receiving flotufolastat F 18.
* Diagnosis of polymetastatic (newly diagnosed prostate cancer and more than five metastatic sites outside of the pelvis or metastatic sites in brain or liver.)
* 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).
* 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).
* Patients with history or evidence of chronic hepatitis B virus (HBV) infection (unless HBV viral load is undetectable on suppressive therapy).
* 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).
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
* Any contraindications to undergo PSMA-PET.
* Clinically significant uncontrolled illness.
* 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.
* 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.
* 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).

Where this trial is running

Duarte, California

• City of Hope Medical Center — Duarte, California, United States (Recruiting)

Study contacts

• Principal investigator: Rose Li, MD, PhD — City of Hope Medical Center
• Study coordinator: Rose Li, MD, PhD

Conditions Prostate Cancer