High Dose Testosterone for Prostate Cancer

(VA-BAT Trial)

Recruiting at 19 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether high-dose testosterone (testosterone therapy) can effectively treat prostate cancer resistant to standard hormone therapy. Researchers aim to determine if this treatment is effective for tumors with specific gene changes (ATM, CDK12, or CHEK2), which might cause instability. Men with metastatic prostate cancer unresponsive to regular hormone treatments, but who are not experiencing severe symptoms, may be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant advancements in prostate cancer therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that high-dose testosterone can be safely administered to patients with prostate cancer unresponsive to standard treatments. In earlier studies, patients tolerated the treatment well without serious side effects. One study found that this treatment did not increase the need for more aggressive therapy or raise the risk of death from prostate cancer.

These results suggest that high-dose testosterone is generally well-tolerated in similar patients. However, individual reactions can vary. Prospective trial participants should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about high dose testosterone treatments for castration-resistant prostate cancer because they offer a unique approach compared to standard hormone therapies, like androgen deprivation therapy. Unlike traditional treatments that lower testosterone levels to slow cancer growth, this approach uses high doses of testosterone to potentially disrupt cancer cell survival mechanisms, especially in patients with specific genetic alterations like CHEK2, ATM, and CDK12. This novel mechanism of action could lead to new ways of managing prostate cancer that doesn't respond to current options, providing hope for improved outcomes for these patients.

What evidence suggests that high dose testosterone might be an effective treatment for prostate cancer?

Research has shown that high-dose testosterone therapy might help treat prostate cancer unresponsive to standard treatments. Studies have found that this method can resensitize cancer cells to hormone treatments. Some patients with prostate cancer have experienced tumor shrinkage when given high-dose testosterone. This trial will treat patients with castration-resistant prostate cancer containing specific gene alterations, such as ATM, CDK12, or CHEK2, with high-dose testosterone to evaluate its effectiveness. Overall, high-dose testosterone appears to be a promising option for addressing challenging cases of prostate cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Robert B Montgomery, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11852443/

Cell Models of Castration Resistant and High Dose ... Simple Summary. High dose testosterone therapy is emerging as a viable treatment strategy for metastatic castration-resistant prostate cancer.

2. hopkinsmedicine.org hopkinsmedicine.org/news/articles/2016/01/for-castrate-resistant-prostate-cancer-high-dose-testosterone

For Castrate-Resistant Prostate Cancer: High-Dose ... The treatment had a double impact: After being bombarded with testosterone, prostate cancer cells were once again susceptible to hormonal ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03734653

Testosterone Therapy in Castration Resistant Prostate ... High dose testosterone has shown activity in phase II studies of patients with castration resistant metastatic prostate cancer; however, these studies have ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666168324002143

Prostate Cancer Oncologic Outcomes of Testosterone ... We found that testosterone therapy did not increase the risk of proceeding to active therapy or of death from prostate cancer.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5108565/

The Role of Testosterone in the Treatment of Castration ... Most men with metastatic prostate cancer who are treated with androgen deprivation therapy will eventually develop castration-resistant disease.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2738932/

Phase 1 Trial of High-Dose Exogenous Testosterone in ... 5. Conclusions. In conclusion, this study shows that high-dose exogenous testosterone can be administered safely to patients with castration-resistant disease.

7. mdpi.com mdpi.com/2075-1729/11/9/884

Titration of Androgen Signaling: How Basic Studies Have ... These trials suggest a clinical benefit in cancer response and quality of life in a subset of castration-resistant prostate cancer patients.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19375217/

Phase 1 trial of high-dose exogenous testosterone in patients ... Conclusions: We have demonstrated that patients with CRMPC can be safely treated in clinical trials using high-dose exogenous testosterone. Patients did not, on ...