Short-term hormone therapy with PSMA PET/CT before prostate removal for high-risk localized prostate cancer

Assessing the Efficacy of Neoadjuvant Androgen Deprivation Therapy (ADT) Utilizing 18F-Flotufolastat PSMA PET/CT in Patients With High-Risk Localized Prostate Cancer (LHRPC)

This trial will test whether giving short-term androgen-deprivation therapy (ADT) before prostate removal lowers PSMA PET signal and helps predict recurrence risk in men with localized high-risk prostate cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Baptist Health South Florida (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Miami, Florida)
• Trial ID: NCT07455903 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase II trial enrolling men with localized high-risk prostate cancer who are planned for radical prostatectomy. Participants will receive neoadjuvant ADT (leuprolide, degarelix, relugolix, or triptorelin, with possible use of bicalutamide) and undergo 18F-Flotufolastat PSMA PET/CT scans before and after ADT to measure changes in SUVmax. The study will correlate post-ADT SUVmax changes with biochemical recurrence-free survival after surgery. Patients will be followed for up to 48 months after prostate removal with blood tests and symptom checks as part of standard care.

Who should consider this trial

Good fit: Men aged 18 or older with histologically confirmed localized high-risk prostate cancer who are candidates for radical prostatectomy, have ECOG 0–1, and are clinically node-negative on PSMA PET/CT are ideal candidates.

Not a fit: Patients with metastatic disease, clearly enlarged lymph nodes meeting conventional size criteria, poor performance status, or who are not planning prostatectomy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could identify men whose tumors respond to short-term ADT on PSMA imaging and help personalize surgical and follow-up plans to reduce recurrence risk.

How similar studies have performed: Previous work has shown neoadjuvant ADT can change PSMA PET uptake, but using 18F-Flotufolastat SUVmax changes to predict long-term outcomes is relatively novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* Males aged ≥18 years.
* ECOG performance status ≤ 1
* Histologically confirmed adenocarcinoma of the prostate in a patient amenable to radical prostatectomy
* Pathologically proven prostate adenocarcinoma with ≥ 1 High-risk feature based on NCCN guidelines.

  1. cT3-cT4
  2. International Society of Urological Pathology (ISUP) Grade group 4 (Gleason score 8) or grade group 5 (Gleason score 9-10)
  3. PSA \>20 ng/mL
* Clinically negative lymph nodes as established by PSMA PET/CT imaging. Patients who are node positive by PSMA PET/CT (e.g., N1), but whose nodes do not meet traditional size criteria for positivity (e.g., they measure ≥ 10mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 and would be eligible for this study.
* Patient is willing to use barrier-method of contraception along with another effective contraceptive method if engaged in sexual activity with a pregnant person or individual of childbearing potential (until 1 week after completing 18F-flotufolastat PSMA PET/CT Scans.
* Clinical laboratory values during screening:

  1. Hemoglobin ≥ 10.0 g/dL
  2. Absolute neutrophil count (ANC) ≥ 1.8 × 10⁹/L
  3. Platelets ≥ 100 × 10⁹/L

Exclusion Criteria:

* Known allergies, hypersensitivity, or intolerance to 18F-flotufolastat.
* Unable to receive androgen deprivation therapy.
* Prostate cancer with significant neuroendocrine or other rare variant pathology
* Evidence of metastatic disease involving bone, viscera, or lymph nodes superior to the bifurcation of the common iliac arteries on PSMA PET/CT
* Renal impairment (glomerular filtration rate \<30 mL/min)
* History of prior radiation therapy for prostate cancer
* Any of the following within 6 months prior to the first dose of study treatment: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, clinically significant ventricular arrhythmias, or New York Heart Association Class II to IV heart disease.
* Uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or untreated HIV infection.
* Other malignancies other than prostate cancer in the past 5 years

  a. Cured basal cell or squamous cell skin cancers can be enrolled.
* Severe or uncontrolled concurrent infections are not eligible.
* Treated with concomitant cytotoxic cancer therapy for any other primary site.
* Patients who are unable to complete the study requirements of 2nd PSMA imaging or surgery for the primary endpoints.
* Any condition that, in the opinion of the investigator, would preclude participation in this study.

Where this trial is running

Miami, Florida

• Miami Cancer Institute at Baptist Health, Inc. — Miami, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Rohan Garje, M.D. — Miami Cancer Institute at Baptist Health, Inc.
• Study coordinator: Rohan Garje, M.D.

Conditions Prostate Cancer; Localized Prostate Carcinoma