Ipilimumab + Abiraterone Acetate + Prednisone for Prostate Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining three medications—ipilimumab (an immunotherapy drug), abiraterone acetate, and prednisone—for treating prostate cancer that has metastasized. The goal is to determine if these drugs, when used together, can safely and effectively reduce cancer growth. Patients with prostate cancer that no longer responds to initial treatments and who are new to chemotherapy or immunotherapy may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, the research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group.

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.

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

Research has shown that ipilimumab, a cancer treatment drug, has been tested in patients with advanced prostate cancer. In these studies, patients received ipilimumab following radiotherapy. Researchers closely monitored the safety of ipilimumab. Some patients experienced side effects such as tiredness, diarrhea, and skin rash, but many continued treatment without major issues.

Abiraterone acetate combined with prednisone is a common treatment for prostate cancer. These drugs lower testosterone levels, which can help slow cancer growth. Common side effects include high blood pressure, low potassium levels, and liver issues.

As this study explores new combinations of these drugs, researchers will carefully monitor any side effects. The study is in its early stages, focusing on determining the best dose and ensuring safety. It is important to discuss any concerns with a doctor and understand all potential risks and benefits before deciding to participate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for prostate cancer that typically focus on hormone therapy, Ipilimumab is unique because it works as an immune checkpoint inhibitor. This means it helps the immune system recognize and attack cancer cells more effectively by targeting CTLA-4, a protein that normally keeps immune responses in check. Researchers are excited about this approach because it could enhance the body's natural defenses against cancer, offering a new way to combat prostate cancer beyond traditional methods like chemotherapy or hormone therapy. Combining Ipilimumab with Abiraterone Acetate and Prednisone might also provide a synergistic effect, potentially improving outcomes for patients with metastatic castration-resistant prostate cancer.

What evidence suggests that this combination treatment could be effective for prostate cancer?

Research has shown that combining abiraterone acetate and prednisone effectively treats prostate cancer by reducing testosterone levels, which the cancer needs to grow. This combination is already a standard treatment and helps manage the disease. In this trial, participants will receive ipilimumab, which boosts the immune system and has shown promise in controlling prostate cancer. Some studies found that patients experienced a longer period where their cancer did not worsen. However, ipilimumab alone hasn't consistently helped all patients live longer. This study investigates whether combining ipilimumab with abiraterone acetate and prednisone could be more effective against prostate cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel Danila, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

I am currently on hormone therapy for cancer.

My cancer has spread beyond the pelvic region, confirmed by scans.

Exclusion Criteria

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

I have a serious heart condition.

I have had major surgery or radiation therapy recently.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/nct02279862

Safety and Efficacy Study of Ipilimumab 3 mg/kg Versus ... The purpose of this study is to examine the safety and effectiveness (how well the drug works) of two different doses (3 mg/kg and 10 mg/kg) of Ipilimumab ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8428575/

Final Analysis of the Ipilimumab Versus Placebo Following ... The phase 3 trial CA184–043 evaluated radiotherapy to bone metastases followed by Ipilimumab or placebo in men with metastatic castrate-resistant prostate ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.69.1584

Randomized, Double-Blind, Phase III Trial of Ipilimumab ... Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0923753424039991

Ipilimumab with nivolumab in molecularly selected patients ... This trial of dual ICIs in molecularly selected mCRPC met its primary endpoint, showing DCR > 6 in 38% of patients.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3707423/

results from an open-label, multicenter phase I/II study - PMC In mCRPC patients, ipilimumab 10 mg/kg ± radiotherapy suggested clinical antitumor activity with disease control and manageable AEs.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)52176-7/fulltext

Updated Overall Survival (Os) from the Phase 3 Trial, ... The phase 3 trial, CA184-043, evaluated OS with radiotherapy (RT) followed by Ipi or Pbo in patients (pts) with advanced mCRPC.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1535610820304189

Article Nivolumab Plus Ipilimumab for Metastatic Castration ... CheckMate 650 is an ongoing open-label, multi-cohort trial evaluating the efficacy and safety of nivolumab plus ipilimumab in patients with ...

8. news.bms.com news.bms.com/news/corporate-financial/2019/Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Shows-Response-in-Pre-Treated-Patients-with-Metastatic-Castration-Resistant-Prostate-Cancer/default.aspx

Opdivo (nivolumab) Plus Yervoy (ipilimumab) Shows ... Opdivo (nivolumab) Plus Yervoy (ipilimumab) Shows Response in Pre-Treated Patients with Metastatic Castration-Resistant Prostate Cancer.