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

17 Participants Needed

Trial Summary

What is the purpose of this trial?

Adaptive Androgen Deprivation Therapy (ADT) plus Standard of Care. The purpose of this study is to develop adaptive therapy for high risk metastatic castration sensitive prostate cancer (mCSPC).

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.

What data supports the effectiveness of the drug Abiraterone in treating advanced prostate cancer?

Research shows that adding Abiraterone acetate with prednisone to androgen deprivation therapy (ADT) significantly improves survival and delays disease progression in men with advanced prostate cancer, both in newly diagnosed and previously treated cases. ^{1 2 3 4 5}

Is androgen deprivation therapy with abiraterone and prednisone safe for humans?

Abiraterone acetate, used with prednisone, is generally considered safe for treating advanced prostate cancer, but it can cause side effects like low potassium levels, high blood pressure, fluid retention, and liver issues. These side effects were relatively low in frequency in clinical trials. ^{4 5 6 7 8}

How is the drug Abiraterone with ADT and Prednisone unique for advanced prostate cancer?

This drug combination is unique because Abiraterone, taken orally, blocks a specific enzyme (cytochrome P450 17A1) that helps produce male hormones, and when combined with Prednisone and ADT, it significantly improves survival in patients with advanced prostate cancer compared to other treatments. ^{2 4 5 9 10}

Research Team

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

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

References

1. England 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. [2023]

2. England 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. [2023]

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

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. [2023]

4. England 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. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

6. United States 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. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022]

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

Abiraterone acetate versus nonsteroidal antiandrogen with androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer. [2022]

10. England 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. [2019]