Androgen Deprivation Therapy for Advanced Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: GnRH analogs

Must not be taking: TAK-700, Ketoconazole

Disqualifiers: CNS metastases, Liver metastasis, others

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

Compensation: Varies

Number of Visits: 10

Duration: Up to 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to develop a flexible treatment plan for men with advanced prostate cancer that has spread but remains sensitive to hormone therapy. It tests a combination of therapies, including abiraterone (also known as Zytiga or Yonsa), prednisone, and hormone treatments, to evaluate their combined effectiveness. Men with prostate cancer who have experienced significant drops in their PSA levels (a protein related to prostate health) after initial treatment might be suitable candidates for this study. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking any investigational drugs, you must stop them at least 30 days before starting the trial.

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

Research has shown that abiraterone, a treatment for prostate cancer, is usually well-tolerated. Most patients experience some side effects, but these are often mild. One study found that serious side effects were less common in patients taking abiraterone (64.1%) compared to those receiving standard care (71.8%).

Adaptive Androgen Deprivation Therapy (ADT) is a common treatment for prostate cancer and has been shown to help patients live longer. However, specific side effects from this adaptive approach have not been widely reported yet.

Prednisone, often used with abiraterone, is considered safe at low doses. Studies indicate that taking prednisone at 5 mg twice a day is generally safe, though some side effects can occur. Overall, these treatments have shown promise in other trials, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for advanced prostate cancer because it employs an adaptive approach to Androgen Deprivation Therapy (ADT), which is different from traditional continuous hormone therapy. Unlike standard treatments that consistently suppress testosterone, this method adapts based on the individual's testosterone and PSA levels, potentially reducing side effects and improving quality of life. Additionally, it combines abiraterone and prednisone, which work together to more effectively block androgen production, offering a potentially more powerful response against cancer cells. This dynamic approach could lead to better management of the disease by personalizing treatment based on patient-specific markers.

What evidence suggests that this trial's treatments could be effective for advanced prostate cancer?

In this trial, participants will receive a combination of treatments. Studies have shown that combining abiraterone with prednisone greatly improves outcomes for patients with advanced prostate cancer. Specifically, patients taking abiraterone experienced an average of 33 months before their cancer worsened, compared to just under 15 months for those on a placebo. Additionally, lower doses of abiraterone are effective, offering a flexible treatment option. Androgen Deprivation Therapy (ADT), another treatment in this trial, reduces male hormone levels and has been used successfully for over 80 years to treat advanced prostate cancer. Combining ADT with modern treatments like abiraterone has led to better management and longer survival for patients. ^{4 6 7 8 9}

Who Is on the Research Team?

Jingsong Zhang, M.D., Ph.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that responds to initial hormone therapy can join. They must be in good physical shape (ECOG 0-1), have normal organ function, and no serious health issues or surgeries in the last month. Excluded are those who've had certain treatments for prostate cancer, uncontrolled high blood pressure, severe heart problems, GI diseases affecting drug absorption, brain or liver metastases, another recent cancer diagnosis or treatment.

Inclusion Criteria

I haven't had any serious health issues or surgeries in the last 28 days.

My prostate cancer was confirmed by a lab test.

My liver, kidney, and blood tests are within normal ranges.

Exclusion Criteria

I have previously been treated with TAK-700, ketoconazole, apalutamide, or enzalutamide.

My cancer has spread to my brain or liver.

I need opioids to manage my cancer pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Period

Participants undergo 12-16 weeks of GnRH analog, along with 8-12 weeks of combinational therapy with GnRH analog and abiraterone plus prednisone

12-16 weeks

PSA and testosterone level measured every 4 weeks

Treatment

Study treatment is restarted if participant's PSA reaches 2 fold or higher of his baseline PSA. Selection of treatment will be based on participant's testosterone level

Up to 12 months

PSA and testosterone level measured every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• Adaptive Androgen Deprivation Therapy (ADT)
• Prednisone

Trial Overview The trial is testing Adaptive Androgen Deprivation Therapy (ADT) combined with standard care including abiraterone and prednisone. The goal is to see if this adaptive approach better controls high-risk metastatic castration-sensitive prostate cancer compared to traditional methods.

How Is the Trial Designed?

Group I: Adaptive ADT+ Standard of Care Experimental Treatment 3 Interventions

Participants will undergo 12-16 weeks of GnRH analog, along with 8-12 weeks of combinational therapy with GnRH analog and abiraterone plus prednisone. 14 participants who achieve \>75% PSA decline after the run-in period will be enrolled. GnRH analog and abiraterone will be stopped after study enrollment. PSA and testosterone level will be measured every 4 weeks during the run-in period, then every 6 weeks after study enrollment. Imaging studies with CT and bone scan will be performed at the time of study enrollment and these will be considered baseline scans. Study treatment will be restarted if participant's PSA reaches 2 fold or higher of his baseline PSA. Selection of treatment will be based on participant's testosterone level.

Abiraterone is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a study involving 1974 men with high-risk non-metastatic prostate cancer, combination therapy with abiraterone acetate and prednisolone significantly improved metastasis-free survival compared to androgen-deprivation therapy (ADT) alone, with a hazard ratio of 0.53, indicating a 47% reduction in the risk of metastasis.

The combination therapy also showed significant improvements in overall survival, prostate cancer-specific survival, and biochemical failure-free survival, although it was associated with a higher incidence of grade 3 or higher adverse events, such as hypertension and liver enzyme elevation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a systematic review of randomized controlled trials involving newly diagnosed patients with metastatic hormone-sensitive prostate cancer, the combination of abiraterone acetate (AA), prednisone (P), and androgen deprivation therapy (ADT) showed a 72% to 87% probability of improving overall survival compared to docetaxel (DOC) plus ADT.

The AA + P + ADT regimen not only reduced the risk of disease progression more effectively (with a 93%-97% probability) but also improved quality of life for patients, particularly noticeable within the first three months of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: A network meta-analysis. Feyerabend, S., Saad, F., Li, T., et al.[2019]

In the final analysis of the LATITUDE study involving 1199 men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer, the combination of abiraterone acetate plus prednisone with androgen deprivation therapy (ADT) significantly improved overall survival, with a median of 53.3 months compared to 36.5 months for the placebo group.

The treatment had a manageable safety profile, with common grade 3-4 adverse events including hypertension and hypokalaemia, indicating that while there are risks, the benefits of improved survival support the use of this combination therapy as a standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Fizazi, K., Tran, N., Fein, L., et al.[2020]

In a study involving 1917 men with locally advanced or metastatic prostate cancer, the combination of abiraterone acetate and prednisolone with androgen-deprivation therapy (ADT) significantly improved overall survival compared to ADT alone, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

The combination therapy also resulted in a much lower rate of treatment failure, with a hazard ratio of 0.29, meaning patients were less likely to experience disease progression compared to those receiving only ADT, although it was associated with a higher incidence of grade 3 to 5 adverse events (47% vs. 33%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. James, ND., de Bono, JS., Spears, MR., et al.[2023]

In a phase 3 trial involving 1199 patients, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly improved overall survival, with a median survival not reached in the abiraterone group compared to 34.7 months in the placebo group.

The study also showed that patients receiving abiraterone had a median radiographic progression-free survival of 33.0 months, compared to 14.8 months in the placebo group, indicating a strong benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi, K., Tran, N., Fein, L., et al.[2022]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38629249/

Predicting abiraterone efficacy in advanced prostate cancer This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.367

Real-world discontinuation and efficacy data of abiraterone ... Background: Data from STAMPEDE trial confirmed Overall survival benefit for patients with high-risk localized or locally advanced prostate ...

3. urologytimes.com urologytimes.com/view/lower-dose-of-abiraterone-shows-comparable-efficacy-to-standard-dose-for-prostate-cancer

Lower dose of abiraterone shows comparable efficacy to ... A 500 mg dose of abiraterone acetate showed comparable efficacy to the standard 1000 mg dose in prostate cancer treatment, with a favorable ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704174

Abiraterone plus Prednisone in Metastatic, Castration- ... The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1130634325001023

Low-dose abiraterone acetate for the treatment of prostate ... This study provides evidence supporting the use of low-dose abiraterone in patients with metastatic prostate cancer, showing survival and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40940844/

The Safety of Abiraterone Acetate in Patients with Metastatic ... Nearly all participants experienced at least one adverse event (98.4% abiraterone, 97.3% standard of care [SOC]).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00485303?term=AREA%5BInterventionSearch%5D(YONSA)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=6

An Efficacy and Safety Study of Abiraterone Acetate and ... The purpose of this study is to evaluate the efficacy and safety of abiraterone acetate in participants with advanced prostate cancer (a disease in which ...

8. mdpi.com mdpi.com/2072-6694/17/17/2747

The Safety of Abiraterone Acetate in Patients with ... More serious adverse events (grade 3 or 4) and deaths (grade 5) occurred in those receiving SOC (71.8%) compared to abiraterone (64.1%). The most frequent ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5053

Real-world comparative effectiveness and cardiovascular ... Conclusions: The long-term comparative effectiveness and cardiovascular safety of abiraterone and enzalutamide were similar, though a short-term ...