Androgen Ablation + Abiraterone/Prednisone for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Androgen ablation

Must not be taking: Hormonal therapy, Chemotherapy

Disqualifiers: Metastases, Heart disease, Viral hepatitis, 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

Compensation: Varies

Number of Visits: 3

Duration: 8 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests treatments for prostate cancer that has returned after initial treatment. The goal is to determine if adding the drugs abiraterone acetate (Zytiga) and prednisone to hormone therapy can better control the cancer. Hormone therapy lowers androgen levels, which helps slow cancer cell growth. This trial targets individuals with prostate cancer recurrence after surgery or radiation, indicated by rising PSA levels, but without visible metastases in scans. Participants will receive either hormone therapy alone or with additional drugs to assess which is more effective. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on long-term corticosteroids or have had certain treatments for prostate cancer, you may not be eligible. It's best to discuss your specific medications with the trial team.

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

Research shows that abiraterone acetate, when combined with prednisone, is usually well-tolerated by patients with prostate cancer. One study found that serious side effects occurred less frequently in those taking abiraterone than in those receiving standard treatments. Specifically, 64.1% of patients on abiraterone experienced serious side effects, compared to 71.8% of patients on standard treatments.

Abiraterone and prednisone have been shown to help patients live longer without their cancer worsening. However, some patients may discontinue this combination early due to side effects in real-world situations.

For those considering hormone therapy drugs like leuprolide acetate or goserelin acetate, research indicates these are commonly used and generally safe for prostate cancer. However, like any treatment, they can have some side effects. Patients should consult their doctor to determine if these options are suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments being studied because they combine traditional androgen deprivation therapy with newer agents like abiraterone acetate and prednisone. Abiraterone acetate works differently from standard options by inhibiting an enzyme involved in producing androgens, which fuel prostate cancer growth. This approach targets cancer more comprehensively than traditional therapies that only block androgen receptors. Adding prednisone helps manage potential side effects and enhances the effectiveness of abiraterone, offering a promising new strategy for battling prostate cancer.

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

Research has shown that taking abiraterone acetate with prednisone can help prostate cancer patients live longer without their cancer worsening. One study found that patients who took these medications experienced a longer time before cancer progression—33 months compared to 14.8 months for those who did not. In this trial, some participants will receive this combination as part of Arm B, which also includes androgen ablation therapy. Meanwhile, treatments like leuprolide acetate or goserelin acetate, part of Arm A, lower the body's androgen levels, slowing cancer growth. Together, these treatments offer promising options for managing recurrent prostate cancer. ^{2 3 5 6 7}

Who Is on the Research Team?

Christopher Logothetis

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Men with recurrent prostate cancer after surgery or radiation, without metastases, are eligible for this trial. They must have a life expectancy of at least 12 months, be in good physical condition (ECOG <=2), and have rising PSA levels. Participants need normal blood counts and organ function tests, agree to use contraception if sexually active, and be able to take oral medication on an empty stomach.

Inclusion Criteria

White blood cell (WBC) >= 3.5 x 10^9/L

Written Authorization for Use and Release of Health and Research Study Information obtained

Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

Exclusion Criteria

Known allergies, hypersensitivity, or intolerance to study drug components

Significant co-morbidity affecting safety or evaluability

Inability to comply with study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive finite androgen ablation with or without abiraterone acetate and prednisone for 8 months

8 months

Monthly visits for injections and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Follow-up visits every 3 and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Bicalutamide
• Goserelin Acetate
• Leuprolide Acetate
• Nilutamide
• Prednisone

Trial Overview

The study is testing the effectiveness of hormone therapy using drugs like leuprolide acetate against prostate cancer growth by lowering androgen levels. It's comparing standard treatment with additional abiraterone acetate (which decreases testosterone production) and prednisone (to reduce side effects).

How Is the Trial Designed?

Group I: Arm B (finite androgen ablation, abiraterone, prednisone) Experimental Treatment 8 Interventions

Participants receive leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide as in Arm A. Patients also receive abiraterone acetate PO daily for 8 months and prednisone daily. Patients may crossover to Arm A with disease progression after 8 months.

Group II: Arm A (finite androgen ablation) Active Control 6 Interventions

Participants receive either leuprolide acetate via injection every month or every 4 months, goserelin acetate via injection every month, or degarelix via injection every month for 8 months. Patients also receive bicalutamide PO QD, flutamide PO TID, or nilutamide PO QD. Patients may crossover to Arm B with disease progression after 8 months.

Abiraterone Acetate 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
• Metastatic high-risk castration-sensitive prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in Japan as Zytiga for:

• Prostate cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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 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 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 phase 3 trial with 1088 patients, abiraterone acetate plus prednisone significantly improved overall survival compared to placebo plus prednisone, with a median survival of 34.7 months versus 30.3 months, indicating its efficacy in treating chemotherapy-naive castration-resistant prostate cancer.

The treatment was associated with a manageable safety profile, although there were some increased risks of grade 3-4 adverse events, such as cardiac disorders and elevated liver enzymes, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Ryan, CJ., Smith, MR., Fizazi, K., et al.[2022]

In a study of 217 patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC) who had previously been treated with abiraterone acetate plus prednisone, no significant differences in overall survival or time to treatment failure were found between those receiving chemotherapy and those receiving non-chemotherapy treatments.

The results indicate that subsequent treatment options after abiraterone acetate plus prednisone can be selected based on physician discretion and patient preference, as both chemotherapy and non-chemotherapy options appear to have similar efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of First Subsequent Therapies After Abiraterone Acetate Plus Prednisone for High-Risk Metastatic Castration-Sensitive Prostate Cancer in the LATITUDE Study. Koroki, Y., Taguri, M.[2023]

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]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

In a study of 131 patients with high-risk, nonmetastatic, castration-resistant prostate cancer, treatment with abiraterone acetate and prednisone resulted in an impressive 86.9% of patients achieving a 50% or greater reduction in prostate-specific antigen (PSA) levels, indicating strong efficacy.

The treatment also showed promising secondary outcomes, with a median time to PSA progression of 28.7 months, while safety was generally acceptable, although 96.2% of patients experienced adverse events, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The IMAAGEN Study: Effect of Abiraterone Acetate and Prednisone on Prostate Specific Antigen and Radiographic Disease Progression in Patients with Nonmetastatic Castration Resistant Prostate Cancer. Ryan, CJ., Crawford, ED., Shore, ND., et al.[2021]

In a study of 1199 men with metastatic castration-sensitive prostate cancer, treatment with abiraterone acetate plus prednisone (AA+P) significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) compared to placebo, particularly in patients with lung metastases.

Patients with visceral metastases (VM) who received AA+P had a median OS of 55.4 months versus 33.0 months for those on placebo, and a median rPFS of 30.7 months compared to 18.3 months, indicating that AA+P is an effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: A post-hoc exploratory analysis of the LATITUDE study. Baciarello, G., Özgüroğlu, M., Mundle, S., 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]

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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 ...