Abiraterone + Prednisone + Apalutamide for Prostate Cancer

Overseen By Paul Corn

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Antiandrogens

Must not be taking: Antidepressants, Antivirals

Disqualifiers: Small cell prostate cancer, Hypertension, Heart disease, 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: 30

Duration: 12 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well abiraterone acetate, prednisone, and apalutamide work in treating patients with hormone-naive prostate cancer that has spread to other places in the body. Androgen can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate and apalutamide may lessen the amount of androgen made by the body.

Will I have to stop taking my current medications?

The trial requires that medications known to lower the seizure threshold be stopped or replaced at least 4 weeks before starting the study. Additionally, if you are on anti-androgens with LHRH agonists, these must be stopped within 2 weeks before starting the trial.

What data supports the effectiveness of the drug combination Abiraterone, Prednisone, and Apalutamide for prostate cancer?

Research shows that Abiraterone combined with Prednisone improves survival and delays disease progression in men with metastatic prostate cancer, especially when used with androgen deprivation therapy. Although Apalutamide is not directly mentioned in these studies, it is another drug used to treat prostate cancer, suggesting potential benefits when combined with Abiraterone and Prednisone. ^{1 2 3 4 5}

Is the combination of Abiraterone, Prednisone, and Apalutamide safe for humans?

Abiraterone combined with prednisone is generally safe for treating prostate cancer, but it can sometimes cause liver issues and hormonal imbalances. Patients may experience increased liver enzymes and conditions like mineralocorticoid excess (too much of certain hormones) and adrenal insufficiency (not enough hormone production by the adrenal glands). ^{2 6 7 8 9}

What makes the drug combination of Abiraterone, Prednisone, and Apalutamide unique for prostate cancer?

This drug combination is unique because it combines Abiraterone and Apalutamide, which both target androgen (male hormone) pathways, with Prednisone, a steroid that helps manage side effects, potentially offering a more comprehensive approach to treating prostate cancer compared to using these drugs separately. ^{1 3 6 7 10}

Research Team

Paul Corn

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Men with hormone-naive metastatic prostate cancer who can perform daily activities with some limitations (ECOG <=2) and have certain high-risk factors like a Gleason score >=8. They must not have small cell prostate cancer, heart issues, or conditions increasing bowel perforation risk. Participants need to be able to take oral medication and agree to use contraception.

Inclusion Criteria

My platelet count is at least 100,000 without transfusions in the last 3 months.

I stopped taking any medication that could increase my risk of seizures 4 weeks ago.

Serum bilirubin < 1.5 x institutional upper limit of normal (IULN) (except for patients with known Gilbert's disease if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible)

Exclusion Criteria

I have had limited treatment for my metastatic prostate cancer before starting this trial.

I have untreated spinal cord compression that causes symptoms.

I do not have an active infection or a condition that prevents steroid use. I do not have HIV/AIDS.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abiraterone acetate, prednisone, and apalutamide. Cycles repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity.

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Follow-up at 30 days and then up to 6 months

Treatment Details

Interventions

• Abiraterone Acetate
• Apalutamide
• Prednisone

Trial Overview The trial is testing the combination of abiraterone acetate, prednisone, and apalutamide in treating men whose prostate cancer has spread but haven't had hormonal treatments yet. The goal is to see if these drugs can reduce the body's production of hormones that fuel tumor growth.

Participant Groups

Group I: Treatment (abiraterone acetate, prednisone, apalutamide) Experimental Treatment 3 Interventions

Patient receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Cycles repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity.

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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]

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 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 multicenter early-access trial involving 2314 patients with metastatic castration-resistant prostate cancer, abiraterone acetate combined with prednisone showed a median time to PSA progression of 8.5 months and a median time to clinical progression of 12.7 months, indicating its efficacy in delaying disease progression after chemotherapy.

The study reported that 41% of patients experienced grade 3 or 4 treatment-related adverse events, with hepatotoxicity and hypertension being the most common, but no new safety signals were identified, suggesting that abiraterone acetate is generally safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial. Sternberg, CN., Castellano, D., Daugaard, G., et al.[2022]

In a clinical trial involving 164 men with metastatic castration-resistant prostate cancer, abiraterone acetate combined with prednisone (5 mg twice daily) or dexamethasone (0.5 mg once daily) effectively minimized mineralocorticoid excess, which is important for patient safety.

While abiraterone with dexamethasone showed promising efficacy, it was also linked to adverse metabolic effects, such as increased insulin resistance and decreased bone mineral density, highlighting the need for careful monitoring of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study. Attard, G., Merseburger, AS., Arlt, W., et al.[2022]

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 study of 25 men with metastatic prostate cancer, liver function test increases were observed while on abiraterone treatment, typically occurring within the first two months of therapy.

Despite these increases, liver toxicity was generally mild, with most patients experiencing a return to normal liver function either spontaneously or after dose adjustments, indicating that abiraterone is relatively safe regarding liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver tests increase on abiraterone acetate in men with metastatic prostate cancer: Natural history, management and outcome. Colomba, E., Marret, G., Baciarello, G., et al.[2020]

Abiraterone, when used with prednisone, improves overall and disease-free survival in patients with both castration-resistant and castration-sensitive prostate cancer.

In a case series of 3 patients, it was found that abiraterone can lead to mineralocorticoid excess and secondary adrenal insufficiency, highlighting the need for awareness and management of these endocrine side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone-Induced Endocrinopathies. Decamps, S., Lis, R., Ekanayake, P.[2023]

In a study involving 202 patients with metastatic castration-resistant prostate cancer, the sequence of treatment with abiraterone acetate followed by enzalutamide resulted in a longer time to second PSA progression (19.3 months) compared to the reverse sequence (15.2 months), indicating a more effective treatment strategy.

Enzalutamide demonstrated a significantly higher PSA response rate (36%) as a second-line therapy compared to abiraterone (4%), suggesting that enzalutamide is more effective when used after abiraterone in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Khalaf, DJ., Annala, M., Taavitsainen, S., et al.[2021]

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

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

3. England 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. [2022]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial. [2022]

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

Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study. [2022]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Liver tests increase on abiraterone acetate in men with metastatic prostate cancer: Natural history, management and outcome. [2020]

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

Abiraterone-Induced Endocrinopathies. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. [2021]