A Phase II, Open-Label Study to Assess Safety and Management Change Using Ga-68-THP PSMA PET/CT in Patients with High-Risk Primary Prostate Cancer or Biochemical Recurrence After Radical Treatment: The PRONOUNCED Study

Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of Ga-68-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason score >= 4 + 3, or PSA >20 ng/mL or clinical stage >T2c. Group B: biochemical recurrence (BCR) and eligible for salvage treatment after radical prostatectomy with two consecutive rises in prostate specific antigen (PSA) with a three month interval in between reads and final PSA >0.1 ng/mL or a PSA level >= 0.5 ng/mL. Group C: BCR with radical curative radiotherapy or brachytherapy at least three months prior to enrolment, and an increase in PSA level >2.0 ng/mL above the nadir level after radiotherapy or brachytherapy. Patients underwent evaluation with PET/CT 60 minutes following intravenous administration of 160 +/- 30 MBq of Ga-68-THP PSMA. Safety was assessed by means including vital signs, cardiovascular profile, serum haematology, biochemistry, urinalysis, PSA, and Adverse Events (AEs). A change in management was reported when the predefined clinical management of the patient altered as a result of Ga-68-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT; 20 in Group A, 21 in Group B and 8 in Group C. No patients experienced serious AEs discontinued the study due to AEs, or died during the study. Two patients had Treatment Emergent AEs attributed to Ga-68-THP-PSMA (pruritus in one patient and intravenous catheter site rash in another). Management change secondary to PET/CT occurred in 42.9% of all patients; 30% in Group A, 42.9% in Group B and 75% in Group C. Conclusion: Ga-68-THP PSMA was safe to use with no serious AE and no AE resulting in withdrawal from the study. Ga-68-THP PSMA PET/CT changed the management of patients in 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned Phase III study of Ga-68-THP PSMA in patients with prostate cancer.