Apalutamide + Abiraterone for Prostate Cancer

(PANTHER Trial)

No longer recruiting at 13 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Daniel George, MD

Must be taking: LHRH agonists or antagonists

Must not be taking: Azole antifungals, Strong CYP3A4 inducers

Disqualifiers: Infection, Hypertension, Diabetes, Seizure, 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: 16

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two medications, apalutamide and abiraterone acetate, in treating prostate cancer that has spread and become resistant to standard hormone therapy. Researchers focus on the impact of these drugs on cancer progression and assess side effects, particularly in African American and Caucasian men. Participants must have prostate cancer that no longer responds to hormone therapy and a rising PSA level, a protein often used to monitor prostate cancer. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

You may need to stop certain medications before joining the trial. Specifically, medications that lower the seizure threshold must be stopped or replaced at least 4 weeks before starting the study. Additionally, you need to avoid strong CYP3A4 inducers and be cautious with certain CYP2D6 substrates during the trial.

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

Research shows that the combination of apalutamide, abiraterone acetate, and prednisone is generally safe for patients. Studies have found that the safety results for this combination align with earlier research, and no new safety concerns have emerged. This indicates that the treatment does not cause unexpected problems.

In one study, patients did not experience any new safety issues, with side effects similar to those already known for these medications. Common side effects may include fatigue or high blood pressure, but these can be managed.

While these medications are approved for treating prostate cancer in other contexts, the current study examines their use together in a specific group of patients. Researchers continue to collect information to fully understand the treatment's safety and effectiveness for everyone involved. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for prostate cancer?

Researchers are excited about the combination of Apalutamide and Abiraterone for prostate cancer because it offers a new way to tackle the disease more effectively. Unlike the standard treatments, which often focus on either blocking testosterone production or its action, this combo addresses both simultaneously. Apalutamide works by blocking androgen receptors, while Abiraterone inhibits an enzyme crucial for testosterone production. This dual action could potentially lead to better control of the cancer and improved outcomes for patients.

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

This trial will evaluate the combination of apalutamide and abiraterone acetate for prostate cancer. Studies have shown that using apalutamide with abiraterone acetate can extend the lives of prostate cancer patients. Specifically, apalutamide is associated with a 26% lower risk of death compared to using abiraterone alone. This combination treatment effectively reduces prostate-specific antigen (PSA) levels, a positive indicator in managing prostate cancer. Apalutamide and abiraterone work together to block hormones that promote cancer growth, slowing the disease's progression. Previous patients have also experienced longer survival with this treatment combination. Overall, these findings suggest that this treatment could effectively manage prostate cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Daniel J. George, MD

Principal Investigator

Duke Cancer Institute

Are You a Good Fit for This Trial?

This trial is for African American and Caucasian men with metastatic castrate-resistant prostate cancer. Participants must be over 18, have a life expectancy of at least 12 months, and be able to take oral medication. They should not have had certain previous treatments or conditions that could interfere with the study drugs or pose risks.

Inclusion Criteria

Serum potassium ≥ 3.5 mEq/L

Serum total bilirubin ≤ 1.5 x Institutional ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)

Serum albumin of ≥ 3.0 g/dl

Exclusion Criteria

I have symptoms due to an irregular heartbeat.

- Administration of an investigational therapeutic within 30 days prior to Cycle 1, Day 1

I have had chemotherapy or biological therapy for prostate cancer, but not within the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apalutamide, abiraterone acetate, and prednisone in 4-week cycles

24 months

Visits every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 4 years

Imaging every 12 weeks, survival follow-up every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Apalutamide
• Prednisone

Trial Overview The trial tests apalutamide, abiraterone acetate, and prednisone in treating prostate cancer. It's an open-label study where both African American and Caucasian men receive the same treatment to compare progression-free survival (PFS) rates, PSA response, radiographic assessments, safety, and tolerability.

How Is the Trial Designed?

Group I: Caucasian Experimental Treatment 3 Interventions

Group II: African American Experimental Treatment 3 Interventions

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?

Daniel George, MD

Lead Sponsor

Trials

8

Recruited

250+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

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

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40340441/

a head-to-head analysis of real-world patients in the USA Apalutamide was associated with a 26% reduction in the risk of mortality compared with abiraterone acetate by 24 months post-treatment initiation.

3. 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 ...

4. 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– ...

5. targetedonc.com targetedonc.com/view/real-world-survival-outcomes-in-mcspc-comparison-of-apalutamide-and-abiraterone

Real-World Survival Outcomes in mCSPC: Comparison of ... Overall, apalutamide may lead to better survival rates than abiraterone in patients with mCSPC. Further studies are needed to confirm these findings.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40327314/

Real-world clinical outcomes of apalutamide versus ... Apalutamide demonstrated deeper and more sustained PSA reductions, translating into delayed disease progression compared to abiraterone.

7. jnj.com jnj.com/media-center/press-releases/janssen-provides-update-on-phase-3-acis-study-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-erleada-apalutamide-and-zytiga-abiraterone-acetate-plus-prednisone-combination

Janssen Provides Update on Phase 3 ACIS Study ... “Safety results from ACIS were consistent with prior studies of ERLEADA and ZYTIGA plus prednisone, with no new safety signals observed.

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

Efficacy and safety of apalutamide, abiraterone acetate ... Results: This study analyzed 146 mHSPC patients. The results are displayed that Apalutamide and Abiraterone significantly prolonged PFS and PSA- ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02867020?term=APALUTAMIDE&rank=1

Study of Abiraterone Acetate Plus ADT Versus ... Evaluation of the activity, safety and patients reported outcome of ADT plus abiraterone, abiraterone plus APALUTAMIDE (a second-generation antiandrogen) or ...