JNJ-56021927 + Abiraterone for Prostate Cancer

Recruiting at 6 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Aragon Pharmaceuticals, Inc.

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

57 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate potential drug-drug interaction (DDI) between JNJ-56021927 and abiraterone acetate and between JNJ-56021927 and prednisone, determine safety of the combination and evaluate in a descriptive manner the efficacy in these participants. It will also, potentially provide dosing recommendations for abiraterone acetate in future studies when combined with JNJ-56021927.

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.

What data supports the effectiveness of the drug JNJ-56021927 + Abiraterone for Prostate Cancer?

Research shows that abiraterone acetate, when used with prednisone, significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer. This combination has been approved by the FDA and has shown positive results in clinical trials. ^{1 2 3 4 5}

Is the combination of JNJ-56021927 and Abiraterone safe for humans?

Abiraterone acetate, when used with prednisone, has been generally well-tolerated in men with metastatic castration-resistant prostate cancer, though it can cause low potassium levels, high blood pressure, fluid retention, and liver issues. The most serious side effects were relatively rare in clinical trials. ^{1 2 3 4 5}

What makes the drug combination of JNJ-56021927 and Abiraterone Acetate unique for prostate cancer treatment?

The combination of JNJ-56021927 and Abiraterone Acetate is unique because it targets prostate cancer by combining a novel drug (JNJ-56021927) with Abiraterone Acetate, which is already known to prolong survival in patients with metastatic castration-resistant prostate cancer. This combination may offer a new approach by potentially enhancing the effectiveness of existing treatments. ^{2 3 5 6 7}

Research Team

Aragon Pharmaceuticals, Inc. Clinical Trial

Principal Investigator

Aragon Pharmaceuticals, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

3. United States 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. [2018]

4. Sweden 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. [2017]

5. Germany 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Duration of Treatment in Prostate Cancer Patients Treated with Abiraterone Acetate or Enzalutamide. [2023]