Combination Therapy for Prostate Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Cyp17-lyase inhibitors, AR antagonists

Disqualifiers: Active infection, Uncontrolled hypertension, Autoimmune 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: 17

Duration: Up to 39 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of treatments to better manage castration-resistant prostate cancer that has spread. Researchers are testing medications like abiraterone acetate (Zytiga) and apalutamide (Erleada), which reduce androgen levels—hormones that can stimulate cancer—along with prednisone. Potential additions include ipilimumab (Yervoy, an immunotherapy) or chemotherapy drugs cabazitaxel (Jevtana) and carboplatin (Paraplatin or Carboplatinum). The goal is to determine if these combinations can more effectively stop cancer growth and spread. Men with prostate cancer that has become resistant to traditional hormone treatments and has spread to other areas might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer care.

Will I have to stop taking my current medications?

The trial requires that certain medications be stopped or substituted at least 4 weeks before starting, especially those that lower the seizure threshold. Additionally, any systemic therapy for prostate cancer, except specific allowed treatments, must be stopped 28 days before starting the trial.

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

Research has shown that combining abiraterone acetate, prednisone, and apalutamide is generally safe and well-tolerated for patients with prostate cancer. One study found that most patients continued treatment without major issues. However, long-term use of prednisone may increase the risk of weak bones and fractures.

For the combination of cabazitaxel and carboplatin, clear safety data is not yet available. These chemotherapy agents are known to cause side effects such as tiredness and low blood cell counts.

In the treatment group with ipilimumab, safety data remains limited. Ipilimumab, an immunotherapy, can cause immune-related side effects ranging from mild to serious.

As this is a Phase 2 trial, these treatments have passed initial safety tests, but ongoing studies will confirm how well these combinations are tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine existing therapies in novel ways to enhance effectiveness. The combination of abiraterone acetate, apalutamide, and prednisone, used in Arm 2A, builds on standard hormone therapies to potentially improve outcomes by more effectively blocking male hormones that fuel cancer growth. Arm 2B introduces ipilimumab, an immunotherapy drug, which may help the body's immune system better target cancer cells, offering a unique approach compared to traditional treatments. Arm 3 includes cabazitaxel and carboplatin, which are chemotherapy agents, to potentially address cancer that is less responsive to hormone treatments, providing a comprehensive attack on cancer cells. These combinations aim to target prostate cancer more aggressively than standard treatments, offering hope for improved patient outcomes.

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

Research has shown that a combination of abiraterone acetate, prednisone, and apalutamide can be promising for treating prostate cancer. Studies have found that these medications can reduce the risk of death by 26% over two years. In this trial, one group will receive this combination alone. Another group will receive the same combination with cabazitaxel and carboplatin, which might enhance benefits by killing cancer cells or stopping their growth. A third group will include ipilimumab, a type of immunotherapy, which could help the immune system find and attack cancer cells, possibly leading to better results. Overall, existing evidence supports the effectiveness of these drug combinations in managing prostate cancer that has spread and is resistant to standard hormone therapy. ^{6 7 8 9 10}

Who Is on the Research Team?

Ana Aparicio

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that is resistant to castration and has spread, who can provide consent, have adequate organ function (blood counts, liver enzymes), and are not on certain medications. They must have a low testosterone level due to surgery or ongoing treatment, be able to swallow pills, agree to use contraception if necessary, and allow tissue collection for studies.

Inclusion Criteria

My cancer outside of bones is growing or new.

Presence of metastatic disease documented on imaging studies (bone scan, computed tomography [CT] and/or magnetic resonance imaging [MRI] scans)

Serum albumin >= 3.0 g/dL

Exclusion Criteria

I have active or symptomatic viral hepatitis or chronic liver disease.

I haven't taken specific prostate cancer drugs or chemotherapy in the last year.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Phase

Patients receive abiraterone acetate, prednisone, and apalutamide for 8 weeks to assess serum marker decline

8 weeks

Weekly visits for monitoring

Treatment

Patients are assigned to different arms based on serum marker decline and receive various combinations of drugs

Up to 39 weeks

Every 3 weeks for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Follow-up at 14 and 30 days, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Apalutamide
• Cabazitaxel
• Carboplatin
• Ipilimumab
• Prednisone

Trial Overview The trial tests how well abiraterone acetate, prednisone, and apalutamide work together compared with the addition of ipilimumab or cabazitaxel plus carboplatin. It aims to see which combination is more effective in stopping tumor growth by reducing androgens or killing tumor cells directly.

How Is the Trial Designed?

Group I: Arm 2B (abiraterone acetate, prednisone, ARN-509, ipilimumab) Experimental Treatment 5 Interventions

Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive ipilimumab IV over 90 minutes on day 1 of courses 4-7. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.

Group II: Arm 2A (abiraterone acetate, prednisone, apalutamide) Experimental Treatment 4 Interventions

Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily in the absence of disease progression or unexpected toxicity.

Group III: Arm 3(abiraterone, prednisone, ARN509,cabazitaxel,carboplatin) Active Control 6 Interventions

Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive cabazitaxel IV over 60 minutes and carboplatin IV, over 60 minutes on day 1 of courses 4-13. Courses repeat every 3 weeks in the absence of disease progression or unexpected 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+

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 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 involving 515 patients with hormone-sensitive prostate cancer, those receiving abiraterone acetate plus prednisone (AAP) alongside standard care reported a higher quality of life (QOL) compared to those receiving docetaxel plus standard care, with a mean difference of +3.9 points over two years.

The improvement in global-QOL scores for the AAP group was particularly significant during the first year, with increases of +5.7 points at one year and +8.3 points at two years, indicating that AAP may offer better patient-reported outcomes in terms of quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial. Rush, HL., Murphy, L., Morgans, AK., 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]

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 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 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]

In a phase II study involving 41 men with metastatic castration-resistant prostate cancer, increasing the dose of abiraterone acetate from 1000 mg to 2000 mg daily did not result in any significant clinical benefit, as no patients showed a prostate-specific antigen (PSA) decline of 30% or more after 12 weeks.

The study found that factors such as lower baseline circulating androgen levels and individual differences in drug metabolism may contribute to resistance against standard-dose abiraterone therapy, suggesting that simply increasing the dose is not an effective strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Friedlander, TW., Graff, JN., Zejnullahu, K., et al.[2018]

In a study of 148 patients with metastatic castration-resistant prostate cancer, maintaining abiraterone acetate plus prednisone (AAP) during docetaxel treatment did not improve radiographic progression-free survival compared to docetaxel plus prednisone alone, with rates of 34.9% and 33.9% respectively after 12 months.

The combination of docetaxel and AAP resulted in significantly higher rates of severe neutropenia (59.6%) compared to docetaxel plus prednisone (27.7%), suggesting that continuing AAP may increase treatment-related risks without providing additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II randomised trial of abiraterone acetate plus prednisone in combination with docetaxel or docetaxel plus prednisone after disease progression to abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer: The ABIDO-SOGUG trial. Climent, MA., Font, A., Durán, I., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12224120/

Overall survival in patients with metastatic castration ... Apalutamide was associated with a 26% reduction in the risk of mortality compared with abiraterone acetate by 24 months post-treatment initiation.

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. targetedonc.com targetedonc.com/view/abiraterone-prednisone-apalutamide-improves-prostate-cancer-outcomes-leaves-hrqol-unaffected

Abiraterone, Prednisone, Apalutamide Improves Prostate ... Oncological outcomes improved with the addition of abiraterone acetate (Zytiga) plus prednisone (AAP) and apalutamide (Erleada) after radical prostatectomy.

4. jnjmedicalconnect.com jnjmedicalconnect.com/products/erleada/medical-content/erleada-comparison-of-erleada-with-zytiga

Comparison of ERLEADA with ZYTIGA By 24 months postindex, patients initiated on ERLEADA had a statistically significant reduction of 26% in the risk of death when compared with patients ...

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00148-1/fulltext

Abiraterone acetate plus prednisolone with or without ... In conclusion, enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy; but ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427571/

The Safety of Abiraterone Acetate in Patients with ... Abiraterone is often given in combination with prednisone, and the long-term use of prednisone is also known to increase the risk of osteoporosis and fractures ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02257736

Study Details | NCT02257736 | An Efficacy and Safety ... The purpose of this study is to compare the radiographic progression-free survival (rPFS) of apalutamide in combination with abiraterone acetate (AA) plus ...

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1656216/full

Efficacy and safety of apalutamide, abiraterone acetate ... Moreover, Apalutamide and Abiraterone showed superior efficacy in improving PSA response compared to Bicalutamide. Importantly, no life- ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5543693/

Safety and Antitumor Activity of Apalutamide (ARN-509) in ... Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC with 80% of AAP-naïve and 43% of post-AAP patients remaining on treatment for ...

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

Abiraterone plus Prednisone in Metastatic, Castration- ... The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic ...