Clinical Trials /

Bipolar Androgen Therapy (BAT) and Radium-223 (RAD) in Metastatic Castration-resistant Prostate Cancer (mCRPC)

NCT04704505

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Bipolar Androgen Therapy (BAT) and Radium-223 (RAD) in Metastatic Castration-resistant Prostate Cancer (mCRPC)
  • Official Title: Bipolar Androgen Therapy (BAT) and Radium-223 (RAD) in Metastatic Castration-resistant Prostate Cancer (mCRPC) (BAT-RAD Study)

Clinical Trial IDs

  • ORG STUDY ID: IRB00273010
  • SECONDARY ID: J2116
  • NCT ID: NCT04704505

Conditions

  • Prostate Adenocarcinoma
  • Metastatic Prostate Adenocarcinoma
  • Castration-resistant

Interventions

DrugSynonymsArms
Bipolar Androgen Therapy (BAT)Bipolar Androgen Therapy in addition to RADium-223 (RAD)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Bipolar Androgen Therapy in addition to RADium-223 (RAD)ExperimentalParticipants will receive Bipolar Androgen Therapy (BAT) plus Radium-223 (RAD).
  • Bipolar Androgen Therapy (BAT)

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  Castrate-resistant prostate cancer, in the setting of castrate levels of testosterone
             (≤ 50 ng/dL), defined as current or historical evidence of disease progression
             concomitant with surgical castration or androgen deprivation therapy (ADT), as
             demonstrated by two consecutive rises in PSA OR new lesions on bone scan:

          -  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

          -  Patients must be on bone health agents, either zoledronic acid or denosumab, for at
             least 4 weeks before enrollment. These treatments must then be continued during the
             study.

          -  Screening Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

          -  Asymptomatic or minimally symptomatic disease (no opioids)

          -  Prior treatment with no more than one novel AR targeted drug (abiraterone,
             enzalutamide, darolutamide or apalutamide) is permitted, but not required. Prior
             first-generation AR targeted therapies such as bicalutamide or nilutamide are
             permitted as previous therapy and does not count as novel AR targeted therapy.

          -  Prior chemotherapy for hormone-sensitive prostate cancer (given ≥ 12 months prior to
             study entry) is allowed, but not necessary.

          -  Adequate bone marrow, renal and liver function (Absolute Neutrophil count > 1,000,
             Platelets >100,000, Hemoglobin ≥ 9g/dL aspartate aminotransferase/ alanine amino
             transferase (AST)/(ALT) within normal limits (WNL); Total Bilirubin WNL.

          -  No evidence (within 5 years) of prior malignancies (except successfully treated basal
             cell or squamous cell carcinoma of the skin).

          -  All patients must have tissue for genomic analysis. A biopsy of a metastatic site may
             be done during the screening; however, archive tissue will be allowed. Prostate tissue
             from prostate biopsy will be allowed.

        Exclusion Criteria:

          -  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.

          -  Systemic therapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the
             treatment of bony metastases within previous 24 weeks

          -  Use of opioid analgesics for cancer-related pain such as oxycodone, morphine or
             methadone. Weak opioid analgesics such as codeine or tramadol are permitted.

          -  Use of experimental drug within 4 weeks of treatment.

          -  Patients with an intact prostate AND urinary obstructive symptoms are excluded (which
             includes patients with urinary symptoms from benign prostatic hyperplasia (BPH).

          -  Patients receiving anticoagulation therapy with warfarin are not eligible for study.
             Patients on other anticoagulants such as rivaroxaban, dabigatran, apixaban are
             permitted.

          -  Symptomatic nodal disease, i.e. scrotal, penile or leg edema.

          -  Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant
             systemic disease, or active, uncontrolled infection or a disease that may compromise
             safety. Examples include, but are not limited to, diabetes, heart failure, chronic
             obstructive pulmonary disease (COPD), ulcerative colitis, or Crohn's disease, Paget's
             disease, ventricular arrhythmia, recent (within 12 months) myocardial infarction,
             thromboembolic events or any psychiatric disorder that prohibits obtaining informed
             consent. Any medical intervention, any other condition, or any other circumstance
             which, in the opinion of the investigator, could compromise adherence with study
             requirements or otherwise compromise the study's objectives.

          -  Evidence of disease in sites or extent that, in the opinion of the investigator, would
             put the patient at risk from therapy with testosterone (e.g. femoral metastases with
             concern over fracture risk, severe and extensive spinal metastases with concern over
             spinal cord compression, etc). Patients with low volume visceral metastasis are
             permitted at the discretion of the investigator, however bone disease must be
             predominant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Radiographic progression-free survival (rPFS) of BAT-RAD
Time Frame:24 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:PSA decline ≥ 50 percent rate (PSA50) of BAT-RAD
Time Frame:24 months
Safety Issue:
Description:To determine the PSA decline ≥ 50% rate (PSA50) of BAT-RAD in patients with mCRPC in 24 months.
Measure:Change in alkaline phosphatase of BAT-RAD
Time Frame:Baseline and then on day one of each cycle (each cycle is 28 days), up to 9 cycles
Safety Issue:
Description:To determine if the dynamics (change) of alkaline phosphatase of BAT-RAD in patients with mCRPC.
Measure:PSA progression-free survival (PSA-PFS) of BAT-RAD
Time Frame:24 months
Safety Issue:
Description:To determine the PSA progression-free survival (PSA-PFS) of BAT-RAD in patients with mCRPC in 24 months.
Measure:Time to disease progression of BAT-RAD
Time Frame:24 months
Safety Issue:
Description:To determine the time to disease progression of BAT-RAD in patients with mCRPC measured in months.
Measure:Overall survival of BAT-RAD
Time Frame:24 months
Safety Issue:
Description:To determine the overall survival of BAT-RAD in patients with mCRPC in 24 months.
Measure:Symptomatic skeletal event-free survival
Time Frame:24 months
Safety Issue:
Description:To determine the symptomatic skeletal event-free survival in patients with mCRPC in 24 months.
Measure:Change in Quality of life as assessed by anxiety/depression EuroQol 5 dimensions 3 levels (EQ-5D-3L)
Time Frame:Baseline, cycle 4 day 1, cycle 7 day 1 and at the end of treatment, up to 28 days post cycle 9 (each cycle is 28 days)
Safety Issue:
Description:The EQ-5D-3L is made up of 5 questions each with 3 levels. The lowest level being none and the highest level being extreme. Overall score range of 3-15 with higher scores signifying worse quality of life.
Measure:Change in Quality of life as assessed by the Functional Assessment of Cancer Therapy- Prostate (FACT-P)
Time Frame:Baseline, cycle 4 day 1, cycle 7 day 1 and at the end of treatment, up to 28 days post cycle 9 (each cycle is 28 days)
Safety Issue:
Description:The (FACT-P) is made up of 39 question the scoring is between 0 and 156 with 0 being the best and 156 as the worst.
Measure:Change in Quality of life as assessed by the Brief Pain Inventory-Short Form (BPI-SF)
Time Frame:Baseline, cycle 4 day 1, cycle 7 day 1 and at the end of treatment, up to 28 days post cycle 9 (each cycle is 28 days)
Safety Issue:
Description:The Brief Pain Inventory-Short Form (BPI-SF) is 1 question 0 being the best and 10 being the worst.
Measure:Safety of BAT-RAD in patients with mCRPC as assessed by number of participants removed for adverse events
Time Frame:Up to 10 months
Safety Issue:
Description:To determine the safety of BAT-RAD in patients with mCRPC in patients with mCRPC compared with standard of care treatment for this patient population. This will be measured through Physical assessment, adverse events and labs and will be measured by how many patients are removed for adverse events.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last Updated

May 26, 2021