Ipilimumab + Abiraterone Acetate + Prednisone for Prostate Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Abiraterone, Prednisone, Ipilimumab

Must not be taking: Antiandrogens, Ketoconazole

Disqualifiers: Other malignancy, Cardiovascular disease, Autoimmune disease, Brain metastasis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

57 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out what effects, good and/or bad, taking ipilimumab with abiraterone acetate plus prednisone has on the patient and the prostate cancer. Abiraterone acetate plus prednisone are drugs that lower testosterone (testosterone stimulates prostate cancer growth). Abiraterone acetate plus prednisone is a treatment for patients with prostate cancer. Abiraterone acetate plus prednisone has not been used together with ipilimumab before. This study will test how they work together. Each patient will receive abiraterone acetate, prednisone and ipilimumab.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does prohibit the use of certain antiandrogens and other agents. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Ipilimumab has shown activity in prostate cancer, especially in men with lower disease burden, suggesting it might be more effective when used early. Abiraterone acetate plus prednisone has been proven to improve survival in men with metastatic prostate cancer, indicating its effectiveness in combination therapies. ^{1 2 3 4 5}

What is known about the safety of Ipilimumab, Abiraterone Acetate, and Prednisone for prostate cancer?

Ipilimumab, also known as Yervoy, can cause immune-related side effects like diarrhea, liver inflammation, and lung issues, which are generally manageable with standard treatments. Abiraterone Acetate combined with Prednisone has been studied for prostate cancer, and while it can improve outcomes, it also requires monitoring for side effects. Overall, these treatments have known safety profiles, but they can cause side effects that need to be managed carefully. ^{2 6 7 8 9}

What makes the drug combination of Ipilimumab, Abiraterone Acetate, and Prednisone unique for prostate cancer treatment?

This drug combination is unique because it includes Ipilimumab, an immune-boosting drug that helps the body's immune system attack cancer cells, alongside Abiraterone Acetate and Prednisone, which are used to lower testosterone levels and manage inflammation, respectively. This combination aims to enhance the body's natural defenses while targeting hormone pathways involved in prostate cancer. ^{10 11 12 13 14}

Research Team

Daniel Danila, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Men aged 18+ with advanced prostate cancer that has spread beyond the pelvic region and is resistant to hormone therapy. They must be chemotherapy and immunotherapy-naïve, have a life expectancy of at least 6 months, and a good performance status. Excluded are those with other cancers in the last 5 years, certain blood or liver conditions, recent major surgery or radiation, autoimmune diseases, brain metastasis, active infections contraindicating prednisone use, significant heart disease or uncontrolled high blood pressure.

Inclusion Criteria

I am 18 or older and can give my consent.

I have metastatic CRPC and haven't received chemotherapy or immunotherapy.

I am currently on hormone therapy for cancer.

Exclusion Criteria

I have had major surgery or radiation therapy recently.

I have not taken antiandrogen medication in the last 4 weeks.

I don't have any major health issues besides cancer that would stop me from joining the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead in Therapy

Participants receive abiraterone acetate plus prednisone for 2 cycles to assess for adverse events

6 weeks

Every 4 weeks for PSA assessment

Combination Therapy

Participants receive ipilimumab in combination with abiraterone acetate plus prednisone

8 months

Every 3 weeks for PSA assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ipilimumab

Trial Overview The trial investigates the combination of Ipilimumab (an immune system booster) with Abiraterone Acetate plus Prednisone (hormonal drugs lowering testosterone which feeds prostate cancer growth). This study aims to determine how well these medications work together for patients who haven't had chemo or immunotherapy before.

Participant Groups

Group I: ipilimumab Experimental Treatment 1 Intervention

This multi-institution open label study has a Phase 1 and Phase 2 component. The Phase 1 dose escalation stage is to establish the tolerability of ipilimumab to be used in combination with the standard clinical dose of abiraterone acetate plus prednisone in chemotherapy and immunotherapy-naïve patients with progressive metastatic CRPC. Due to the overlapping potential hepatic toxicity between abiraterone and ipilimumab, a Lead in Therapy with abiraterone plus prednisone for 2 cycles will assess for adverse events related to the abiraterone plus prednisone. Patients, who tolerate well the Lead in therapy as defined by Grade 1 or less AEs, will pursue Combination Therapy. Patients with AEs Grade ≥ 2 after Lead in Therapy will be excluded and replaced. The Phase 2 stage will assess efficacy and confirm an acceptable safety profile of the recommended dose.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Findings from Research

In a phase II study involving 69 patients with metastatic castration-resistant prostate cancer, the combination of sipuleucel-T with abiraterone acetate plus prednisone (AA + P) did not negatively affect the immune responses or the manufacturing of sipuleucel-T, indicating that these treatments can be safely administered together.

Both concurrent and sequential administration of AA + P showed significant immune activation, suggesting that sipuleucel-T retains its immunologic benefits even when combined with other therapies, and the combination was well tolerated without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer. Small, EJ., Lance, RS., Gardner, TA., et al.[2016]

Ipilimumab, a monoclonal antibody targeting CTLA-4, has shown potential activity in prostate cancer, particularly in patients with lower disease burden, despite not improving overall survival in a Phase III study.

While immune-related adverse events are common with ipilimumab treatment, they can generally be managed effectively using standard immunosuppressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab in the treatment of prostate cancer. Reese, Z., Straubhar, A., Pal, SK., et al.[2018]

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]

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 review of 129 oncology patients treated with immune checkpoint inhibitors, 51.9% experienced at least one immune-related adverse event (irAE), highlighting the common occurrence of these side effects.

Nearly half of the irAEs were managed according to established guidelines, but there was significant variability in documentation and management practices, indicating a need for improved adherence as immunotherapy use increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events. Teimouri, A., Minard, LV., Scott, SN., et al.[2022]

In the IPATential150 trial involving 1097 patients with metastatic castration-resistant prostate cancer, adding ipatasertib to abiraterone and prednisone significantly improved radiographic progression-free survival for patients with PTEN-loss tumors.

While ipatasertib was associated with a higher rate of serious adverse events and treatment discontinuation compared to placebo, its overall safety profile was considered tolerable, suggesting that with proper management, the side effects could be mitigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. Matsubara, N., de Bono, J., Sweeney, C., et al.[2023]

Ipilimumab, an anti-CTLA-4 monoclonal antibody, is a significant advancement in cancer immunotherapy, effectively targeting T-cell inhibitory checkpoints to enhance the immune response against tumors.

In a review of 44 prostate cancer patients treated with ipilimumab, it was found that while the therapy is effective, it is also associated with immune-related adverse events (irAEs) that require careful management with immunosuppressive agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience. Gao, J., He, Q., Subudhi, S., 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]

The ERA 223 trial found that combining abiraterone with radium-223 did not improve survival free from symptomatic skeletal events in men with chemotherapy-naïve castration-resistant prostate cancer and bone metastases.

The lack of improvement in outcomes may be linked to bone loss caused by the use of prednisone, which was administered alongside the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Risk of Fragility Fractures in Prostate Cancer Patients Treated with Combined Radium-223 and Abiraterone: Prednisone May Be the Culprit. Dalla Volta, A., Formenti, AM., Berruti, A.[2022]

In a pivotal phase III trial, oral abiraterone acetate combined with prednisone significantly improved overall survival and delayed disease progression in patients with metastatic castration-resistant prostate cancer (CRPC) who had previously undergone docetaxel chemotherapy.

While abiraterone acetate showed a generally acceptable safety profile, it was associated with higher rates of specific adverse events, such as cardiac disorders and fluid retention, compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: in metastatic castration-resistant prostate cancer. Yang, LP.[2021]

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 involving 497 patients with castration-resistant prostate cancer in Japan, abiraterone acetate plus prednisolone demonstrated a safety profile with adverse events occurring in 45.7% of patients, with the most common being abnormal liver function.

The treatment was effective, with 25.5% of patients achieving a significant reduction in prostate-specific antigen levels after 12 weeks, and a 24-month survival rate of 68.3%, which was higher in chemotherapy-naïve patients compared to those who had undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abiraterone acetate plus prednisolone in patients with castration-resistant prostate cancer: a prospective, observational, post-marketing surveillance study. Koroki, Y., Imanaka, K., Yasuda, Y., et al.[2021]

References

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

A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Ipilimumab in the treatment of prostate cancer. [2018]

3. England 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. [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

Combination therapy: Abiraterone prolongs survival in metastatic prostate cancer. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events. [2022]

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

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. [2023]

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

Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience. [2022]

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

Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study. [2021]

10. 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]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Higher Risk of Fragility Fractures in Prostate Cancer Patients Treated with Combined Radium-223 and Abiraterone: Prednisone May Be the Culprit. [2022]

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

Abiraterone acetate: in metastatic castration-resistant prostate cancer. [2021]

13. United States 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. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abiraterone acetate plus prednisolone in patients with castration-resistant prostate cancer: a prospective, observational, post-marketing surveillance study. [2021]