Apalutamide + Abiraterone Acetate for Prostate Cancer

No longer recruiting at 73 trial locations

Overseen By Mary-Ellen Taplin, MD

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Alliance Foundation Trials, LLC.

Must not be taking: CYP17 inhibitors, 5-alpha reductase

Disqualifiers: Androgen deprivation therapy, Seizure, Hypertension, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for men whose prostate cancer has returned after surgery, showing rapid PSA level increases. It tests various combinations of medications, including apalutamide (a hormone therapy) and abiraterone acetate (also known as Zytiga, another hormone therapy), to determine which is most effective. Men who have undergone prostate surgery and experience quick PSA doubling (a measure of cancer activity) might be suitable candidates. The trial aims to identify the best approach to manage and slow the progression of this type of prostate cancer. As a Phase 3 trial, this research represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

You may need to stop taking certain medications to join the trial. Specifically, medications that lower the seizure threshold must be stopped or replaced at least 4 weeks before starting the trial. Additionally, some other medications are not allowed within a week before starting the trial for certain study arms.

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

Research has shown that apalutamide is generally safe and well-tolerated. In various studies, patients experienced good results with only a few serious side effects. For instance, a small number of patients encountered issues with blood flow in the brain, but this was rare. Most patients had positive outcomes.

When combined with abiraterone acetate and prednisone, apalutamide remains mostly safe. Only about 1% of patients experienced serious side effects from this treatment. This combination has improved cancer outcomes without significantly affecting quality of life.

These treatments have been tested in many studies and are considered well-tolerated by most patients. Existing research supports their safety for those considering joining a clinical trial. ^{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 innovative approaches that could enhance effectiveness. Unlike standard hormone therapies like leuprolide or bicalutamide, the combination includes apalutamide, which blocks androgen receptors differently, potentially offering more comprehensive cancer cell suppression. Adding abiraterone acetate helps further reduce androgen production, a key driver of prostate cancer, which might improve outcomes for patients who don’t fully respond to existing treatments. Including prednisone aims to mitigate side effects and enhance treatment tolerability, making the regimen not only potent but also potentially easier for patients to manage.

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

Research has shown that apalutamide effectively treats prostate cancer. In this trial, participants in Arm B will receive apalutamide combined with either degarelix or leuprolide. Arm C will test apalutamide with abiraterone acetate and prednisone, alongside either degarelix or leuprolide. Previous studies indicate that adding apalutamide to abiraterone and prednisone improves outcomes compared to using just abiraterone and prednisone. Specifically, this combination led to more patients experiencing a significant drop in prostate-specific antigen (PSA) levels, indicating reduced cancer activity. These findings suggest that apalutamide, especially when combined with other drugs, can improve survival and manage prostate cancer more effectively. ^{2 5 6 7 8}

Who Is on the Research Team?

Suzanne George, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Men with high-risk, biochemically recurrent prostate cancer and a PSA doubling time of ≤9 months. They must have had prior surgery or radiation, no metastases on scans, an ECOG status of 0-1 (fully active to restricted in physically strenuous activity), and agree to contraception use. Exclusions include previous chemotherapy for prostate cancer (except as neoadjuvant/adjuvant therapy), recent use of certain medications, uncontrolled hypertension, severe liver impairment, and conditions predisposing to seizures.

Inclusion Criteria

I am fully active or can carry out light work.

My blood tests show normal liver, kidney, and blood health.

My scans show no clear signs of cancer spread, except for small lymph nodes or unclear bone lesions.

Exclusion Criteria

I haven't taken 5-alpha reductase inhibitors in the last 42 days.

I have a stomach or intestine condition that affects how I absorb medicine or swallow pills.

I have had chemotherapy for prostate cancer only as part of initial treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients are randomized into one of three treatment arms and treated for a maximum duration of 52 weeks

52 weeks

Follow-up

Participants are monitored for PSA progression, development of metastasis, or patient withdrawal from study

Until PSA progression or other endpoints

Long-term follow-up

Patients with PSA progression will be followed long term until the development of castration resistance, first metastasis, and death

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Apalutamide
• LHRH Analogue
• Prednisone

Trial Overview This phase 3 trial is testing the effectiveness of three different treatment combinations: Apalutamide with LHRH Analogue; Abiraterone Acetate with Prednisone; or both combinations together in men whose prostate cancer has returned but without visible metastasis. Participants are randomly assigned to one of these three groups.

How Is the Trial Designed?

Group I: Arm C: Degarelix/Apalutamide/Abiraterone/Prednisone Experimental Treatment 4 Interventions

Patients will receive apalutamide and abiraterone acetate, in addition to either degarelix OR leuprolide. Patients on this arm will NOT take bicalutamide at any point in the treatment course.

Group II: Arm B: Degarelix/Apalutamide Experimental Treatment 2 Interventions

Patients will receive apalutamide and either degarelix OR leuprolide. Patients on this arm will NOT take bicalutamide at any point in the treatment course.

Group III: Arm A: Degarelix Monotherapy OR Leuprolide/Bicalutamide Active Control 1 Intervention

Patients will receive degarelix OR leuprolide with bicalutamide.

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?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Citations

1. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

2. erleadahcp.com erleadahcp.com/efficacy/

Efficacy | ERLEADA® (apalutamide) HCP Median follow-up time was 44.0 months. 1. The survival rate at 48 months was 65.1% for ERLEADA ® + ADT patients vs 51.8% for placebo + ADT patients.

3. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51– ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39893578/

Real-world clinical usage and efficacy of apalutamide in ... The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124002530

Apalutamide in Metastatic Castration-sensitive Prostate ... Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

6. erleadahcp.com erleadahcp.com/patient-reported-outcomes/

PATIENT-REPORTED OUTCOMES FOR HRQoL 1-6 Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA® and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39613567/

Results from the Multicenter Real-world ARON-3 Study Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1903307

Apalutamide for Metastatic, Castration-Sensitive Prostate ... In our trial, initial therapy with apalutamide in patients with metastatic, castration-sensitive prostate cancer led to improved clinical outcomes. The intent ...