Bipolar Androgen Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must be taking: Androgen ablative therapy

Disqualifiers: Brain metastases, Uncontrolled infection, Thromboembolic event, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called bipolar androgen therapy, which uses testosterone to manage prostate cancer that has spread despite ongoing therapy. The goal is to determine if adjusting testosterone levels can slow cancer growth and reduce prostate-specific antigen (PSA) levels. Participants receive testosterone injections while continuing standard cancer treatment. This trial suits those with prostate cancer progressing despite current treatment and who have had prior therapies, including androgen receptor blockers and chemotherapy. Regular tests, including scans and possibly biopsies, will monitor the treatment's effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had chemotherapy or radiotherapy within 4 weeks before starting the study, which might imply a need to pause certain treatments. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that bipolar androgen therapy (BAT) is generally well-tolerated by patients. In one study, about 40% of patients experienced significant anti-tumor effects with manageable side effects, meaning that while side effects occurred, they were not severe for most individuals. Another study found that patients who completed BAT and then switched to other treatments responded well, suggesting that BAT did not cause long-lasting negative effects. Although more research is needed to fully understand all possible risks, current evidence indicates that BAT is relatively safe for people with advanced prostate cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bipolar Androgen Therapy (BAT) is unique because it flips the script on traditional prostate cancer treatments, which typically focus on reducing testosterone levels. Instead, BAT uses high doses of testosterone to potentially shock cancer cells and disrupt their growth. Researchers are excited about this approach because it might overcome resistance to conventional hormone therapies and offer a new avenue for patients whose cancer no longer responds to standard treatments. By combining this with the ongoing use of leuprolide acetate, a standard hormone therapy, BAT could provide a powerful one-two punch against prostate cancer.

What evidence suggests that bipolar androgen therapy might be an effective treatment for prostate cancer?

Research has shown that Bipolar Androgen Therapy (BAT), the treatment under study in this trial, can help treat prostate cancer that has spread and no longer responds to standard treatments. Studies suggest that BAT may slow the disease by altering how cells react to male hormones like testosterone. One study found that BAT worked better than another treatment, Enza, for men with certain blood markers, delaying the cancer's progression. Another analysis indicated that BAT is safe and effective, especially for patients who haven't had success with other treatments. Overall, early findings suggest BAT might help manage aggressive prostate cancer with a good safety record. ^{3 6 7 8 9}

Who Is on the Research Team?

Gurkamal Chatta, Dr.

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic castration-resistant prostate cancer, which means their cancer has spread and doesn't respond to low testosterone levels. Participants should have a certain level of PSA in their blood and must not have received specific treatments before.

Inclusion Criteria

Total bilirubin: ≤ 1.2 x institutional upper limit of normal (ULN)

Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): ≤ 3 × institutional ULN

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug

Unwilling or unable to follow protocol requirements

Evidence of serious and/or unstable pre-existing medical, psychiatric, or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive testosterone intramuscularly on day 1 of each cycle, with cycles repeating every 28 days for 3 cycles

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up at 30 days and every 3 months for up to 2 years

Up to 2 years

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bipolar Androgen Therapy

Trial Overview The study tests bipolar androgen therapy (BAT) using testosterone to see if it can make the body's cells more sensitive again to hormone treatment. It involves alternating between very low and high testosterone levels, alongside standard care like scans and biopsies.

How Is the Trial Designed?

Group I: Treatment (Bipolar androgen therapy) Experimental Treatment 7 Interventions

Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.

Bipolar Androgen Therapy is already approved in United States for the following indications:

Approved in United States as Bipolar Androgen Therapy for:

• Metastatic Castration-Resistant Prostate Cancer

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

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]

In a study of 30 patients with metastatic castration-resistant prostate cancer who progressed after enzalutamide, 30% achieved a significant reduction in prostate-specific antigen (PSA) levels (PSA50) after treatment with bipolar androgen therapy (BAT), indicating its potential efficacy.

BAT was found to be a safe treatment option, with only a few patients experiencing grade 3-4 adverse events, primarily hypertension, and no treatment-related deaths reported, suggesting a favorable safety profile for further exploration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study. Teply, BA., Wang, H., Luber, B., et al.[2021]

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]

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]

Bipolar androgen therapy (BAT) has been shown to be a safe and effective treatment for castration-resistant prostate cancer (CRPC), with a PSA50 response rate of 27% and an overall response rate of 34% based on a meta-analysis of ten studies involving 108 unique records.

Patients who completed BAT and then received androgen receptor-targeted therapies like abiraterone or enzalutamide achieved a significantly higher PSA50 response rate of 57%, indicating that BAT can help resensitize patients to these treatments after they have previously failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review. You, X., Huang, S., Wang, X., 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9168525/

Clinical Efficacy of Bipolar Androgen Therapy in Men with ... Our data suggest that BAT may induce clinically meaningful responses in aggressive-variant prostate cancers with a more favorable safety profile ...

2. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1125838/full

Efficacy and safety of bipolar androgen therapy in ... The results of this meta-analysis indicate that BAT is a safe and effective treatment for patients who have progressed after Abi or Enz. BAT can ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06305598

Study Details | NCT06305598 | Bipolar Androgen Therapy ... This phase I trial tests the change in androgen receptor sensitivity, side effects and effectiveness of bipolar androgen therapy, using testosterone, ...

4. urotoday.com urotoday.com/library-resources/mcrpc-treatment/154413-bipolar-androgen-therapy-rationale-candidate-patients-and-latest-evidence-for-mcrpc-patients.html

Bipolar Androgen Therapy: Rationale, Candidate Patients ... Prostate cancer cells can develop resistance to androgen ablation through an adaptive marked upregulation of androgen receptors over time in response to low- ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA5014

Blood-based markers of differential efficacy of bipolar ... In men with positive AR alterations detected in blood, BAT was more efficacious than Enza (median PFS 4.2 months vs. 2.9 months; hazard ratio [ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10127253/

Efficacy and safety of bipolar androgen therapy in ... Patients who completed BAT proceeded to AR-targeted therapy (Abi or Enz) and achieved a PSA50 response rate of 57% (95% CI [0.36,0.78], I2=0).

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.178

Extreme bipolar androgen therapy: Alternating ... ExBAT study demonstrated durable (12 months or more) antintumor activity of alternating BAT and darolutamide in around 40% of pts, with manageble safety ...

8. nature.com nature.com/articles/s41467-023-44514-2

Bipolar androgen therapy plus nivolumab for patients with ... After a median follow-up of 17.9 months, the median rPFS was 5.6 (95% CI: 5.4–6.8) months, and median OS was 24.4 (95% CI: 17.6–31.1) months.

9. actr.amegroups.org actr.amegroups.org/article/view/10098/html

The COMBAT trial: use of bipolar androgen therapy to ... Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: results from a pilot clinical study. Sci ...