JNJ-56021927 + Abiraterone for Prostate Cancer

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Aragon Pharmaceuticals, Inc.

Must not be taking: Seizure threshold, PSA reducers

Disqualifiers: Brain metastases, Small cell carcinoma, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how three treatments work together to fight prostate cancer. The main focus is to assess the interaction and safety of abiraterone acetate (Zytiga), prednisone, and JNJ-56021927 (an experimental treatment) when used in combination. Researchers aim to determine the effectiveness of these treatments in managing prostate cancer that has spread to other parts of the body. Individuals with confirmed prostate cancer that has progressed and spread, who are already undergoing hormone therapy, might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new experimental treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you should not take medications that lower the seizure threshold, herbal products like saw palmetto or pomegranate juice, and certain drugs that affect liver enzymes, such as dexamethasone or St. John's wort.

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

Research has shown that apalutamide, also known as JNJ-56021927, often causes mild to moderate side effects, such as skin rashes and itching. Some patients find these side effects improve with a lower dose. Nearly all participants in studies reported some side effects, but these were usually not severe.

Abiraterone acetate, another treatment in this study, is generally well-tolerated. Studies have shown that it causes fewer serious side effects compared to other standard treatments. Many prostate cancer patients, including those with heart problems, have used it successfully.

Both treatments are known to improve outcomes for prostate cancer patients and have FDA approval for certain types of prostate cancer. This approval indicates they have passed safety tests for those uses, suggesting a good level of safety overall. However, researchers are still closely studying the combination with prednisone and any interactions between these drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, which typically focus on reducing testosterone levels, the investigational drug JNJ-56021927 targets the androgen receptor signaling pathway more directly. This is exciting because it could potentially offer a more precise way to disrupt cancer growth. Researchers are also combining JNJ-56021927 with abiraterone acetate and prednisone, hoping this synergy will enhance the treatment's effectiveness. This combination approach aims to tackle cancer cells from multiple angles, potentially leading to better patient outcomes than current therapies alone.

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

Research has shown that combining JNJ-56021927 with abiraterone acetate may help treat prostate cancer. In this trial, participants in both Cohort 1 and Cohort 2 will receive abiraterone acetate and prednisone, followed by JNJ-56021927. Studies have found that abiraterone acetate can significantly extend life and delay cancer progression in men with advanced prostate cancer unresponsive to hormone therapy. When used with JNJ-56021927, the risk of cancer worsening or causing death decreased by 30%. These results suggest that this combination could effectively manage prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Aragon Pharmaceuticals, Inc. Clinical Trial

Principal Investigator

Aragon Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that has spread and is resistant to hormonal therapy can join. They must have low testosterone from treatment, show cancer growth, and have good enough bone marrow and organ function. Men with brain metastases, small cell carcinoma of the prostate, recent other cancer treatments or certain medications are excluded.

Inclusion Criteria

My organs and bone marrow are working well.

My prostate cancer is getting worse.

Documentation of metastatic disease

Exclusion Criteria

My prostate cancer is of the small cell type.

I haven't had chemotherapy or immunotherapy for prostate cancer in the last 4 weeks.

I will stop taking certain medications and supplements before starting treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive abiraterone acetate and prednisone initially, followed by combined intake of AAP + JNJ-56021927 for up to 18 months

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• JNJ-56021927
• Prednisone

Trial Overview

The trial tests how JNJ-56021927 (ARN-509) interacts with abiraterone acetate and prednisone in treating advanced prostate cancer. It aims to establish safety, observe effectiveness, and may suggest doses for future studies when these drugs are combined.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 3 Interventions

Participants will receive abiraterone acetate (AA) along with prednisone on Day 1, Treatment Cycle 1 up to Day 7, Treatment Cycle 1; followed by combined intake of AAP + JNJ-56021927 from Day 8, Treatment Cycle 1 up to the end of treatment (EoT) visit (ie, up to approximately 18 months). On Days 7 and 36, participants will receive AA and prednisone together. On Day 8, Treatment Cycle 2 participants will receive JNJ-56021927, 1 hour after intake of AAP. Treatment cycles will be of 28 days.

Group II: Cohort 1 Experimental Treatment 3 Interventions

Participants will receive abiraterone acetate (AA) along with prednisone on Day 1, Treatment Cycle 1 up to Day 7, Treatment Cycle 1; followed by combined intake of abiraterone acetate + prednisone (AAP) + JNJ-56021927 from Day 8, Treatment Cycle 1 up to the end of treatment (EoT) visit (ie, up to approximately 18 months). On Day 8, Treatment Cycle 2 participants will receive JNJ-56021927, 1 hour after intake of AA and prednisone. Breakfast will be offered approximately 30 minutes after intake of JNJ-56021927. Treatment cycles will be of 28 days.

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?

Aragon Pharmaceuticals, Inc.

Lead Sponsor

Trials

17

Recruited

5,400+

Published Research Related to This Trial

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

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]

In a study of 3,398 patients with metastatic castration-resistant prostate cancer, those initiated on abiraterone acetate (AA) had a significantly longer duration of treatment compared to those initiated on enzalutamide (ENZ), with a median duration of 18.3 months for AA versus 14.2 months for ENZ.

Patients on AA also experienced fewer treatment discontinuations at various time points, indicating that AA may provide a more sustained treatment option for managing prostate cancer compared to ENZ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of Treatment in Prostate Cancer Patients Treated with Abiraterone Acetate or Enzalutamide. Pilon, D., Behl, AS., Ellis, LA., et al.[2023]

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]

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]

Citations

1.

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 ...

2.

yoda.yale.edu

yoda.yale.edu/clinical-trial/nct02257736-a-phase-3-randomized-placebo-controlled-double-blind-study-of-jnj-56021927-in-combination-with-abiraterone-acetate-and-prednisone-versus-abiraterone-acetate-and-prednisone-in-subjects-w/

NCT02257736 - The YODA Project

A Phase 3 Randomized, Placebo-controlled Double-blind Study of JNJ-56021927 in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12427571/

The Safety of Abiraterone Acetate in Patients with ...

Abiraterone acetate is one of the most common drugs used in the treatment of metastatic prostate cancer. As with many therapies, adverse events can occur ...

4.

withpower.com

withpower.com/trial/jnj-56021927-abiraterone-for-prostate-cancer-7b056

JNJ-56021927 + Abiraterone for Prostate Cancer

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate ...

5.

clin.larvol.com

clin.larvol.com/trial-detail/NCT02257736

An Efficacy and Safety Study of Apalutamide (JNJ- ...

According to an updated analysis performed at a median follow-up of 54.8 months, a 30 percent reduction in the risk of radiographic progression or death was ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40940844/

The Safety of Abiraterone Acetate in Patients with Metastatic ...

A real-world prospective study is warranted to examine the overall risks and benefits associated with treatment. Keywords: fracture; metastatic ...

7.

mdpi.com

mdpi.com/2072-6694/17/17/2747

The Safety of Abiraterone Acetate in Patients with ...

More serious adverse events (grade 3 or 4) and deaths (grade 5) occurred in those receiving SOC (71.8%) compared to abiraterone (64.1%). The most frequent ...

8.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/33826036/

Real-World Safety and Efficacy Outcomes with Abiraterone ...

First- and second-line AAP is well tolerated and effective in patients with mCRPC, including those with underlying CV comorbidities.

9.

e-juo.org

e-juo.org/journal/view.php?number=594

Assessing Patient Risk, Benefit, and Outcomes in Drug ...

Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our ...

10.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1209096

Abiraterone in Metastatic Prostate Cancer without Previous ...

Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after ...