ChemoHormonal Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must be taking: Apalutamide, Abiraterone, Prednisone

Must not be taking: Atypical antipsychotics, Tricyclic antidepressants

Disqualifiers: Seizure, Uncontrolled hypertension, Active infection, 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: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of medications, including apalutamide and abiraterone acetate, can effectively treat prostate cancer that has spread and remains responsive to hormone therapy. The researchers aim to determine if these drugs, when used after chemotherapy, can better combat prostate cancer by blocking or reducing testosterone, which fuels cancer growth. The study also seeks to uncover genetic factors that might enhance prostate cancer diagnosis and treatment. Men with prostate cancer that has spread, are sensitive to hormone therapy, and have not yet progressed on hormone treatment might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, medications that lower the seizure threshold and certain psychiatric medications must be stopped or substituted at least 4 weeks before starting the study. Additionally, some herbal agents and specific drugs like first-generation androgen receptor antagonists must be stopped before the trial begins.

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 and well-tolerated for patients with prostate cancer. Studies have found that many patients can continue this treatment without serious side effects. For instance, one study reported that 80% of patients who had not used these treatments before stayed on them without major problems. Another study found that adding apalutamide to abiraterone and prednisone did not harm patients' quality of life, indicating that the treatment is manageable. While all treatments have some risks, current research supports the safety of this combination for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of abiraterone acetate and apalutamide for prostate cancer because these drugs offer a more targeted approach compared to traditional treatments like chemotherapy or standard hormone therapy. Abiraterone acetate works by blocking the production of androgens, which fuel prostate cancer growth, while apalutamide directly inhibits the androgen receptor. This dual action could potentially provide more effective control of the cancer. Additionally, this combination is taken orally, which is more convenient for patients than treatments requiring intravenous administration.

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

In this trial, participants will receive a combination of apalutamide, abiraterone acetate, and prednisone, along with androgen deprivation therapy. Research has shown that combining these medications can effectively treat prostate cancer. Specifically, one study found that adding apalutamide improved results compared to using just abiraterone and prednisone. This combination led to better survival rates and quicker drops in prostate-specific antigen (PSA) levels, which indicate prostate cancer activity. In everyday medical practice, patients who began treatment with apalutamide had a lower risk of death than those who did not. These findings suggest that this treatment could be promising for managing prostate cancer that has spread but still responds to hormone therapy. ^{2 4 6 7 8}

Who Is on the Research Team?

Julie Graff, MD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

Men with high-risk, treatment-naive metastatic prostate cancer that is sensitive to hormone therapy are eligible. They must have completed up to 6 cycles of docetaxel chemotherapy and meet specific criteria including a PSA > 50 ng/mL, certain levels of disease spread, and no prior second-generation antiandrogen therapies. Participants need good organ function, controlled blood pressure without certain medications, no active infections like HIV or hepatitis, and agree to use contraception.

Inclusion Criteria

I have more than 4 bone lesions, with at least one outside my spine or pelvis, or I have cancer that has spread to my organs.

I can take care of myself but might not be able to do heavy physical work.

Patients must have a condition that is considered to be high risk for the study.

Exclusion Criteria

I am not taking specific drugs that don't mix well with the trial medication.

I have had a seizure or a condition that could lead to seizures, like a recent stroke.

I am willing to stop taking saw palmetto or other similar herbal supplements.

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 orally once daily, with cycles repeating every 4 weeks in the absence of disease progression or unacceptable toxicity. Androgen deprivation therapy is also administered per standard of care.

12 months

Monthly visits for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for up to 10 years.

Up to 10 years

Biannual visits

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Apalutamide
• Prednisone

Trial Overview The trial tests the effectiveness of combining apalutamide, abiraterone acetate, and prednisone after chemotherapy in men with advanced prostate cancer. It also investigates genetic factors related to prostate cancer inheritance. The goal is to see if this combination works better for those who haven't had previous treatments and whose cancer still responds to hormone therapy.

How Is the Trial Designed?

Group I: Treatment (apalutamide, abiraterone acetate, prednisone, ADT) Experimental Treatment 8 Interventions

Patients receive apalutamide PO QD, abiraterone acetate PO QD, and prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of care. Patients undergo CT scan, bone scan and blood sample collection throughout the study.

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?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

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

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

In a study of 12 men with metastatic castrate-resistant prostate cancer (mCRPC) who were re-treated with abiraterone acetate (AA), only 46% of those who initially responded to AA showed a similar response upon re-treatment, indicating limited efficacy.

The median duration of response to AA re-treatment was short, with a median biochemical progression-free survival of just 2.3 months, suggesting that re-challenging with AA may not provide significant long-term benefits for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. Leibowitz-Amit, R., Alimohamed, N., Vera-Badillo, FE., et al.[2016]

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]

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]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

Oral abiraterone acetate (Zytiga®) effectively inhibits androgen biosynthesis, which is crucial for the progression of metastatic castration-resistant prostate cancer (mCRPC), and has been shown to prolong overall survival and radiographic progression-free survival in large phase 3 trials.

In combination with prednisone, abiraterone acetate has a manageable safety profile and is a convenient once-daily treatment option, making it a significant first-line therapy for men with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. Scott, LJ.[2019]

Abiraterone acetate is the first second-line hormonal treatment shown to improve survival in metastatic castration-resistant prostate cancer, initially approved in 2011 for patients who had not responded to docetaxel, showing a 4-month survival benefit.

The FDA has expanded its use to the pre-chemotherapy setting due to significant delays in disease progression and trends toward increased overall survival, with ongoing studies investigating its effectiveness in earlier stages and in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: targeting persistent androgen dependence in castration-resistant prostate cancer. Harshman, LC., Taplin, ME.[2021]

Men with advanced prostate cancer taking abiraterone have a significantly higher risk of major metabolic or cardiovascular adverse events compared to those not on the medication, with a hazard ratio of 1.77.

Enzalutamide also increases the risk of major adverse events, but to a lesser extent (hazard ratio of 1.22), and does not significantly increase the risk of minor adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. Lai, LY., Oerline, MK., Caram, MEV., et al.[2023]

Abiraterone acetate (Zytiga®) is an effective antiandrogen for prostate cancer but has poor oral bioavailability (<10%) and requires patients to fast around its administration due to a significant food effect (5-10-fold increase in absorption).

The review highlights the need for improved oral formulation strategies to enhance solubility and bioavailability of abiraterone acetate, aiming to reduce the required dose and eliminate the food effect, which could lead to better patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. Schultz, HB., Meola, TR., Thomas, N., et al.[2020]

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9377412/

Apalutamide plus abiraterone acetate and prednisone in ... The addition of apalutamide to abiraterone-prednisone versus abiraterone-prednisone alone resulted in a significantly higher rate of confirmed ≥ ...

2. 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.

3. becarispublishing.com becarispublishing.com/doi/10.57264/cer-2025-0023

a head-to-head analysis of real-world patients in the USA The results of this study show that compared with abiraterone acetate, initial treatment with apalutamide resulted in better real-world survival ...

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

Survival outcomes of apalutamide as a starting treatment First-line APA + ADT in mHSPC was associated with statistically significantly longer OS, longer TTCR, and faster and deeper PSA responses than other life- ...

5. 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 ...

6. 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 ...

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5015

A prospective trial of apalutamide and abiraterone acetate ... We designed the PANTHER trial to estimate clinical outcomes among Black and White pts with mCRPC treated with apalutamide, abiraterone, plus prednisone.