High Dose Testosterone for Prostate Cancer

(VA-BAT Trial)

Recruiting at 18 trial locations

Overseen By Elahe Mostaghel, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: GnRH analogues

Must not be taking: Opioids

Disqualifiers: Brain metastasis, Liver metastases, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

51 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue your current gonadal androgen deprivation therapy (like GnRH analogues or antagonists) if you haven't had an orchiectomy.

What data supports the effectiveness of high-dose testosterone therapy for prostate cancer?

Recent studies suggest that testosterone therapy can be safe for men with a history of prostate cancer, provided they are disease-free and have good control over their cancer. In a study of 110 patients who had prostate cancer and underwent surgery, only one experienced a recurrence while on testosterone therapy, indicating potential safety and effectiveness in selected cases. ^{1 2 3 4 5}

Is high-dose testosterone therapy safe for humans, especially regarding prostate health?

Testosterone therapy has been used for over 50 years and is generally considered safe, but it can enhance the growth of pre-existing prostate cancer. Regular monitoring of prostate-specific antigen (PSA) levels is recommended, especially in the first year of treatment, to ensure prostate safety. ^{2 6 7 8 9}

How is high-dose testosterone therapy different from other treatments for prostate cancer?

High-dose testosterone therapy is unique because it challenges the traditional belief that testosterone should be avoided in prostate cancer patients. Recent studies suggest that it may be safe and beneficial for men with prostate cancer, especially those with testosterone deficiency, potentially improving their quality of life. ^{5 6 8 10 11}

What is the purpose of this trial?

This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis

Research Team

Robert B Montgomery, MD

Principal Investigator

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Eligibility Criteria

This trial is for men over 18 with advanced prostate cancer that's resistant to hormone therapy. They must be on androgen deprivation treatment, have specific gene mutations (ATM, CDK12, CHEK2), and an ECOG Performance Status <2. Excluded are those with dementia, other cancers being treated, liver metastases or significant heart disease.

Inclusion Criteria

Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following: PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart, Evaluable disease progression by modified RECIST 1.1, Progression of metastatic bone disease on bone scan with > 2 new lesions, Presence of metastatic disease on bone or CT scan, Patients must have progressed on 1 next-generation AR-signaling inhibitor (e.g. abiraterone, enzalutamide, apalutamide, darolutamide, etc.), Asymptomatic or minimal cancer related symptoms, Eastern Cooperative Oncology Group (ECOG) Performance Status of < 2, Presence of inactivating mutations in ATM, CDK12 or CHEK2 as determined by a CLIA level assay for DNA sequencing

My prostate cancer was confirmed by a lab test.

Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information

Exclusion Criteria

I do not have active hepatitis or severe liver disease.

Currently receiving active therapy for other neoplastic disorders will not be eligible

I have brain metastases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high dose testosterone until disease progression or intolerance

12 weeks

Frequent visits for safety and tolerability assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• High dose testosterone

Trial Overview The study tests if high dose testosterone can benefit patients whose prostate cancer has DNA repair deficiencies due to ATM, CDK12 or CHEK2 alterations. It's a prospective study checking the hypothesis that genetically unstable tumors respond well to this treatment.

Participant Groups

Group I: CHEK2 Experimental Treatment 1 Intervention

Patients with castration resistant prostate cancer which contains CHEK2 alterations are treated with high dose testosterone

Group II: CDK12 Experimental Treatment 1 Intervention

Patients with castration resistant prostate cancer which contains CDK12 alterations are treated with high dose testosterone

Group III: ATM Experimental Treatment 1 Intervention

Patients with castration resistant prostate cancer which contains ATM alterations are treated with high dose testosterone

High dose testosterone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Testosterone therapy for:

• Hypogonadism
• Delayed puberty in males

Approved in European Union as Testosterone therapy for:

• Hypogonadism
• Delayed puberty in males

Approved in Canada as Testosterone therapy for:

• Hypogonadism
• Delayed puberty in males

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Testosterone replacement therapy can be safely administered to selected patients with a history of low-risk localized prostate cancer who are disease-free and symptomatic, based on a review of five studies involving 110 patients.

Among these patients, only one experienced a biochemical recurrence during testosterone therapy, suggesting that with proper patient selection and monitoring, the treatment can be effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient with testosterone deficit syndrome after radical prostatectomy]. Linares Espinós, E., Martínez-Salamanca, JI., Morgentaler, A., et al.[2013]

Testosterone therapy can significantly improve well-being, muscle and bone mass, strength, and libido in men with late-onset hypogonadism, but achieving optimal therapy remains challenging due to the limitations of oral testosterone delivery.

While current evidence suggests testosterone therapy is safe, it is crucial to monitor prostate health through digital rectal exams and PSA levels, especially during the first 3-6 months of treatment, to mitigate the risk of promoting pre-existing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of therapy for symptomatic late-onset hypogonadism with transdermal testosterone gel. Ebert, T., Jockenhövel, F., Morales, A., et al.[2013]

Testosterone supplementation in five men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer significantly increased testosterone levels from a mean of 5.2 nmol/L to 17.6 nmol/L over an average follow-up of 14.5 months.

All patients reported improvements in symptoms related to testosterone deficiency, such as reduced hot flushes, decreased fatigue, and enhanced libido, with no serious adverse effects noted, suggesting that testosterone therapy may be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations. Morales, A., Black, AM., Emerson, LE.[2013]

In a study of 96 prostate cancer survivors treated with high-dose testosterone-replacement therapy (TRT), most men experienced increased PSA levels, but stopping TRT often led to declines in PSA levels without additional treatment.

A subset of 31 men continued TRT for a median of 36.7 months without any disease progression, indicating that TRT can be safely managed in certain patients, particularly those with low PSA levels at the start and those who had undergone radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone replacement in prostate cancer survivors with hypogonadal symptoms. Leibowitz, RL., Dorff, TB., Tucker, S., et al.[2015]

Recent literature indicates that testosterone therapy does not increase the risk of prostate cancer or lead to more aggressive disease in men with testosterone deficiency, challenging the long-held belief that higher testosterone levels promote cancer growth.

Men with a history of localized prostate cancer who receive testosterone therapy do not experience higher rates of cancer recurrence or worse outcomes, suggesting that testosterone therapy can be a safe and effective option for managing testosterone deficiency in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Therapy in Men With Prostate Cancer. Kaplan, AL., Hu, JC., Morgentaler, A., et al.[2018]

In a study of 98 hypogonadal men with prostate cancer treated with radiation therapy, testosterone therapy led to a significant increase in serum testosterone levels, from a median of 209 ng/dl to 420 ng/dl, indicating effective treatment.

The therapy was associated with only a minor increase in prostate specific antigen (PSA) levels and a low rate of biochemical recurrence (6.1%), suggesting that testosterone therapy may be safe for men post-radiation treatment for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer. Pastuszak, AW., Khanna, A., Badhiwala, N., et al.[2016]

Exogenous testosterone therapy in hypogonadal men can lead to prostate volumes similar to those of men with normal testosterone levels, with only modest increases in PSA levels and minor changes in urinary flow, suggesting a relatively safe profile for prostate health.

Current evidence indicates that while testosterone does not cause prostate cancer, it can exacerbate existing prostate malignancies; however, there is no causal link between testosterone treatment and the development of prostate cancer in hypogonadal elderly men, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen replacement therapy and prostate safety. Morales, A.[2019]

Testosterone therapy (TTh) can significantly improve the quality of life for men, and concerns about it increasing the risk of prostate cancer or cardiovascular issues are not strongly supported by current evidence.

While the safety of TTh in men with a history of prostate cancer remains uncertain, existing data does not convincingly show that TTh causes or worsens prostate cancer, suggesting that it may be considered for treating hypogonadal men with such a history, albeit with caution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Testosterone Therapy in the Setting of Prostate Cancer. Rodriguez, KM., Pastuszak, AW., Khera, M.[2018]

Testosterone replacement therapy is increasingly prescribed for older men, but concerns exist regarding its long-term risks, particularly related to prostate health, including benign prostatic hypertrophy (BPH) and prostate cancer.

Current data suggest that short-term use of testosterone therapy is relatively safe, but the studies reviewed involved small participant numbers, highlighting the need for larger, long-term studies to fully understand the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of androgen supplementation therapy on the prostate. Kaufman, JM.[2013]

Testosterone levels can provide important insights into the aggressiveness of prostate cancer (PCa), with low testosterone in localized cases indicating a higher likelihood of aggressive disease, suggesting that these patients may not be suitable for active surveillance.

In advanced PCa, maintaining testosterone levels at or below 0.2 ng/mL is crucial for effective androgen deprivation therapy, as this helps ensure proper castration and may influence disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Influence of plasmatic testosterone during natural history of prostate cancer: a review]. Lasselin, J., Drouin, SJ., Champy, CM., et al.[2018]

Recent evidence suggests that testosterone therapy can be safely offered to many men with prostate cancer, challenging the outdated prohibition based on concepts from over 70 years ago.

Men with prostate cancer who have symptoms of testosterone deficiency may experience significant improvements in their quality of life with testosterone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Therapy in a Man with Intermediate-risk Prostate Cancer: Pro. Morgentaler, A.[2021]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Patient with testosterone deficit syndrome after radical prostatectomy]. [2013]

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

The current status of therapy for symptomatic late-onset hypogonadism with transdermal testosterone gel. [2013]

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

Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Testosterone replacement in prostate cancer survivors with hypogonadal symptoms. [2015]

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

Testosterone Therapy in Men With Prostate Cancer. [2018]

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

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer. [2016]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Androgen replacement therapy and prostate safety. [2019]

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

The Role of Testosterone Therapy in the Setting of Prostate Cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

The effect of androgen supplementation therapy on the prostate. [2013]

10. France pubmed.ncbi.nlm.nih.gov

[Influence of plasmatic testosterone during natural history of prostate cancer: a review]. [2018]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Testosterone Therapy in a Man with Intermediate-risk Prostate Cancer: Pro. [2021]