This is a single-arm, multicenter open label, international, phase II study of Bipolar Androgen Therapy (BAT) plus Radium-223 (RAD) in men with metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC with progressive disease (radiographically and/or biochemically) who have been treated with gonadotropin-releasing hormone (GnRH)-analogue (LHRH agonists/antagonists) continuously or bilateral orchidectomy will be enrolled in this study. Previous antiandrogen therapies are permitted, but no more than one (such as abiraterone, enzalutamide, apalutamide, darolutamide). All patients will receive treatment with Radium-223 at a dose of 55 Kilobecquerel (kBq) per kilogram of body weight IV every 28 days, for 6 cycles, plus Testosterone Cypionate 400mg Intramuscular (IM) every 28 days, until progression or unacceptable toxicity.
Histologically documented adenocarcinoma of the prostate confirmed by pathology report from prostate biopsy or a radical prostatectomy specimen. If prostatic tumor is of mixed histology, > 50% of the tumor must be adenocarcinoma.
Bone metastases as manifested by one or more lesions on a Technetium 99m bone scan performed within 2 months of screening
PSA progression will be defined as 2 rising PSA values compared to a reference value, measured at least 7 days apart and the second value is ≥ 2 ng/mL. Appearance of one or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the precastration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression. It must be documented within 8 weeks of screening Documented bone lesions by the appearance of ≥ 2 new lesions by bone scintigraphy or dimensionally measurable soft tissue metastatic lesion assessed by CT or MRI.
Serum PSA ≥ 2.0 ng/mL
The presence of known visceral metastasis, including lung, liver and brain metastases.
Spinal cord compression, imminent long bone fracture, or any other condition that, in the opinion of the investigator, is likely to require radiation therapy and/or steroids for pain control during the active phase.
Previous treatment with chemotherapy for mCRPC, or chemotherapy for any reason within 12 months prior to registration. (Chemotherapy in the adjuvant setting or for hormone-sensitive prostate cancer is permitted, as long as it was completed more than 6 months before registration).
History of radiation therapy, either via external beam or brachytherapy within 28 days prior to registration.
Single group
radium-223
RadiationRadium-223 is an alpha-particle-emitting bone-targeted therapy. All patients will receive Treatment with Radium-223 at a dose of 55 kBq per kilogram of body weight IV every 28 days, for 6 cycles,
Bipolar Androgen Therapy (BAT)
DrugAll Patients will receiveTestosterone Cypionate 400mg IM every 28 days, until progression or unacceptable toxicity.
Radiographic progression-free survival (rPFS) of BAT-RAD
To determine the radiographic progression-free survival (rPFS) of BAT-RAD in patients with mCRPC treated with at least one novel androgen receptor (AR) targeted treatment.
PSA decline ≥ 50 percent rate (PSA50) of BAT-RAD
To determine the PSA decline ≥ 50% rate (PSA50) of BAT-RAD in patients with mCRPC in 24 months.
Change in alkaline phosphatase of BAT-RAD
To determine if the dynamics (change) of alkaline phosphatase of BAT-RAD in patients with mCRPC.
PSA progression-free survival (PSA-PFS) of BAT-RAD
To determine the PSA progression-free survival (PSA-PFS) of BAT-RAD in patients with mCRPC in 24 months.
Time to disease progression of BAT-RAD
To determine the time to disease progression of BAT-RAD in patients with mCRPC measured in months.
Percentage of patients with somatic (tumor) or germline (inherited) mutations
To estimate the percentage of patients with somatic (tumor) or germline (inherited) mutations in homologous repair (HR) and/or mismatch repair (MMR) genes in patients with mCRPC.
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