BAT + Radium-223 for Prostate Cancer

(BAT-RAD Trial)

Recruiting at 2 trial locations

Overseen By Amber Michalik, BA

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: Zoledronic acid, Denosumab

Must not be taking: Opioid analgesics, Warfarin

Disqualifiers: Visceral metastasis, Spinal cord compression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 6 months

47 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must continue taking bone health agents like zoledronic acid or denosumab during the study. If you are on warfarin, you cannot participate, but other anticoagulants are allowed.

What data supports the effectiveness of the treatment BAT + Radium-223 for prostate cancer?

Research shows that bipolar androgen therapy (BAT) can be safely used in men with prostate cancer that no longer responds to standard hormone treatments, with 30%-40% of patients experiencing positive responses. Additionally, BAT may help restore the effectiveness of other prostate cancer treatments. ^{1 2 3 4 5}

Is BAT safe for humans?

Bipolar androgen therapy (BAT) has been shown to be safe in initial studies for men with castration-resistant prostate cancer, with no serious adverse events reported. ^{1 3 5 6 7}

What makes the BAT + Radium-223 treatment unique for prostate cancer?

The BAT + Radium-223 treatment is unique because it combines bipolar androgen therapy (BAT), which involves rapidly alternating testosterone levels, with Radium-223, a radioactive substance that targets bone metastases. This approach not only aims to manage castration-resistant prostate cancer but also potentially restores sensitivity to other treatments and reduces prostate-specific antigen levels. ^{1 2 3 5 6}

Research Team

Samuel Denmeade, M,D

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital

Pedro Isaacsson Velho, M,D

Principal Investigator

Moinhos de Vento Hospital

Eligibility Criteria

Men with advanced prostate cancer that has spread to the bones and is resistant to hormone therapy can join. They should have tried hormone-blocking treatments, but only one newer drug like abiraterone or enzalutamide. No recent chemo for mCRPC, no major health issues unrelated to cancer, and they must not be using strong painkillers like morphine.

Inclusion Criteria

I am fully active or can carry out light work.

I can provide tissue samples for genetic testing.

My PSA levels have increased and I have new bone or soft tissue cancer lesions.

Exclusion Criteria

I have had chemotherapy for advanced prostate cancer or any reason in the last year, but not within the last 6 months if it was for early-stage or hormone-sensitive prostate cancer.

I use strong painkillers like oxycodone for my cancer pain. Weak painkillers like tramadol are okay.

I have a serious health condition that is not well-controlled.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Radium-223 at a dose of 55 kBq/kg IV every 28 days for 6 cycles, plus Testosterone Cypionate 400mg IM every 28 days, until progression or unacceptable toxicity

6 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Bipolar Androgen Therapy (BAT)
• Radium-223

Trial Overview The trial tests a combination of high-dose testosterone injections (BAT) and Radium-223 (RAD), a radioactive drug targeting bone metastases. Participants will receive these treatments every 28 days for up to six cycles, monitoring for disease progression or unacceptable side effects.

Participant Groups

Group I: Bipolar Androgen Therapy in addition to RADium-223 (RAD) Experimental Treatment 2 Interventions

Participants will receive Bipolar Androgen Therapy (BAT) plus Radium-223 (RAD).

Bipolar Androgen Therapy (BAT) is already approved in United States, European Union for the following indications:

Approved in United States as Bipolar Androgen Therapy for:

• None approved; experimental use in clinical trials for metastatic castration-resistant prostate cancer (mCRPC)

Approved in European Union as Bipolar Androgen Therapy for:

• None approved; experimental use in clinical trials for metastatic castration-resistant prostate cancer (mCRPC)

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

Bipolar androgen therapy (BAT) using high-dose testosterone injections is a promising treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), showing clinical activity and potential to resensitize patients to previous androgen receptor-targeted therapies.

Patients who had previously progressed on enzalutamide showed a significantly higher response rate (68%) to AR-targeted therapy rechallenge after BAT compared to those who had progressed on abiraterone (16%), indicating that the type of prior therapy influences the effectiveness of BAT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts. Markowski, MC., Wang, H., Sullivan, R., et al.[2022]

Bipolar androgen therapy (BAT) is a safe treatment option for asymptomatic men with metastatic castration-resistant prostate cancer, showing no symptomatic disease progression during treatment.

BAT has demonstrated the ability to produce sustained responses in 30%-40% of patients and can resensitize them to future antiandrogen therapies, making it a promising strategy for managing resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipolar androgen therapy (BAT): A patient's guide. Denmeade, S., Antonarakis, ES., Markowski, MC.[2022]

In a Phase II trial involving 36 patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of bipolar androgen therapy (BAT) and the PARP inhibitor olaparib resulted in a 31% PSA50 response rate at 12 weeks, indicating significant efficacy in reducing prostate-specific antigen levels.

The treatment also demonstrated a median progression-free survival of 13 months, with clinical benefits observed regardless of the presence of homologous recombination repair (HRR) gene mutations, suggesting that this therapy could be effective for a broad range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer. Schweizer, MT., Gulati, R., Yezefski, T., et al.[2023]

In a study of 114 men with metastatic castration-resistant prostate cancer (mCRPC), 19% achieved significant PSA reductions (≥70%) after treatment with bipolar androgen therapy (BAT), indicating its potential efficacy.

All patients who responded deeply to BAT had mutations in the TP53 gene or homologous recombination DNA repair genes, suggesting that BAT may be particularly beneficial for those with DNA repair deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular and Clinical Characterization of Patients With Metastatic Castration Resistant Prostate Cancer Achieving Deep Responses to Bipolar Androgen Therapy. Markowski, MC., Kachhap, S., De Marzo, AM., et al.[2022]

Bipolar androgen therapy (BAT) is a novel treatment for castrate-resistant prostate cancer that involves alternating testosterone levels between high and low concentrations, which has shown to be safe and effective in initial studies.

A clinical trial is currently underway to compare the efficacy of BAT with enzalutamide, a standard treatment for prostate cancer, highlighting the ongoing research into BAT's potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipolar Androgen Therapy: A Paradoxical Approach for the Treatment of Castration-resistant Prostate Cancer. Schweizer, MT., Antonarakis, ES., Denmeade, SR.[2019]

Bipolar androgen therapy (BAT) has been shown to significantly lower prostate-specific antigen (PSA) levels in patients with castration-resistant prostate cancer (CRPC), indicating its efficacy as a treatment option.

BAT has an excellent safety profile, with no serious adverse events reported in clinical trials, making it a promising therapeutic strategy for managing CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bipolar androgen therapy: A novel therapeutic strategy for castration-resistant prostate cancer]. Hu, YH., Guo, JC., Zhang, M.[2018]

In a study involving 60 men with metastatic castration-resistant prostate cancer, bipolar androgen therapy (BAT) led to significant improvements in body composition, including a mean loss of 7.8% subcutaneous fat, 9.8% visceral fat, and a gain of 12.2% muscle mass after three cycles of treatment.

BAT also resulted in notable enhancements in quality of life measures, such as energy and physical function, suggesting it may be a beneficial treatment option for improving overall health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversing the effects of androgen-deprivation therapy in men with metastatic castration-resistant prostate cancer. Marshall, CH., Tunacao, J., Danda, V., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Bipolar androgen therapy (BAT): A patient's guide. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Molecular and Clinical Characterization of Patients With Metastatic Castration Resistant Prostate Cancer Achieving Deep Responses to Bipolar Androgen Therapy. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Bipolar Androgen Therapy: A Paradoxical Approach for the Treatment of Castration-resistant Prostate Cancer. [2019]

6. China pubmed.ncbi.nlm.nih.gov

[Bipolar androgen therapy: A novel therapeutic strategy for castration-resistant prostate cancer]. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Reversing the effects of androgen-deprivation therapy in men with metastatic castration-resistant prostate cancer. [2023]