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

Trial Summary

What is the purpose of this trial?

This phase I trial tests the change in androgen receptor sensitivity, side effects and effectiveness of bipolar androgen therapy, using testosterone, in patients with castration resistant prostate cancer that has spread to other places is the body (metastatic). Bipolar androgen therapy is the regulation of testosterone between castration levels (lower than what would be normally present) and supraphysiological levels (amounts greater than normally found in the body). This may suppress cancer cell growth, which reduces prostate-specific antigen (PSA) levels and may delay cancer progression.

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.

What data supports the effectiveness of the treatment Bipolar Androgen Therapy (BAT) for prostate cancer?

Research shows that Bipolar Androgen Therapy (BAT) can be safely given to men with prostate cancer that no longer responds to standard hormone treatments. It has been found to reduce prostate-specific antigen (a marker of prostate cancer) levels and produce positive responses in 30%-40% of patients, and it may also help other treatments work better afterwards. ^{1 2 3 4 5}

Is Bipolar Androgen Therapy (BAT) safe for humans?

Bipolar Androgen Therapy (BAT) has been shown to be safe in clinical studies for men with castration-resistant prostate cancer, with no serious adverse events reported. ^{1 2 4 6 7}

How is Bipolar Androgen Therapy different from other treatments for prostate cancer?

Bipolar Androgen Therapy (BAT) is unique because it involves rapidly alternating testosterone levels between very high and very low, which is different from standard treatments that typically aim to lower testosterone. This approach can help resensitize cancer to other therapies and has shown promise in patients with castration-resistant prostate cancer. ^{1 2 4 5 7}

Research Team

Gurkamal Chatta, Dr.

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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 am 18 years old or older.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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) 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 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]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. England 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. [2021]

4. China pubmed.ncbi.nlm.nih.gov

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

5. 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]

6. Switzerland 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. [2023]

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

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