Niraparib + Abiraterone for Prostate Cancer

Recruiting at 20 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: GnRHa therapy

Must not be taking: Prednisone, Prednisolone

Disqualifiers: Brain metastases, MDS/AML, others

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

Compensation: Varies

Number of Visits: 30

Duration: 3 weeks

136 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the relative bioavailability (rBA; Period 1) and bioequivalence (BE; Period 2 and 3) of various strengths and formulations of niraparib and abiraterone acetate (AA) at steady state under modified fasted conditions in participants with metastatic castration-resistant prostate cancer (mCRPC).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you can continue gonadotropin-releasing hormone analogues (GnRHa) therapy if you haven't had a bilateral orchiectomy (surgical removal of both testicles).

What data supports the effectiveness of the drug combination of Niraparib and Abiraterone Acetate for prostate cancer?

The combination of Niraparib with Abiraterone Acetate and Prednisone showed promising effectiveness in patients with metastatic castration-resistant prostate cancer, particularly those with specific genetic alterations, according to the phase II QUEST study. Additionally, Abiraterone Acetate plus Prednisone has been shown to improve survival in men with castration-resistant prostate cancer in the COU-AA-302 trial. ^{1 2 3 4 5}

Is the combination of Niraparib and Abiraterone safe for humans?

The combination of Niraparib with Abiraterone Acetate and Prednisone has shown a manageable safety profile in patients with metastatic castration-resistant prostate cancer. Abiraterone Acetate, when used with Prednisone, is generally well tolerated, though it can cause known side effects like liver issues and effects related to steroid use. ^{2 4 6 7 8}

What makes the drug combination of Niraparib and Abiraterone unique for prostate cancer treatment?

The combination of Niraparib and Abiraterone for prostate cancer is unique because it combines a PARP inhibitor (Niraparib) with a drug that blocks androgen production (Abiraterone), potentially offering a novel approach to targeting cancer cells in patients with specific genetic profiles, unlike standard treatments that typically use Abiraterone with prednisone alone. ^{2 9 10 11 12}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Men with metastatic castration-resistant prostate cancer (mCRPC) who may benefit from the study treatments. Participants should be able to continue hormone therapy if not surgically castrated, have a performance status indicating they are relatively active and can care for themselves, and must provide a tumor sample for genetic testing.

Inclusion Criteria

I can continue hormone therapy during the study if I haven't had surgery to remove my testicles.

I have advanced prostate cancer that is not responding to hormone therapy.

I am fully active or have some restrictions but can still care for myself.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Treatment

Participants receive various formulations of niraparib and abiraterone acetate to assess bioavailability and bioequivalence

3 weeks

Multiple visits for dosing and monitoring

Extension

Participants continue to receive treatment with niraparib and AAP or AAP alone

Until discontinuation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End of treatment visit within 30 days after last dose

Treatment Details

Interventions

• Abiraterone Acetate (AA)
• Niraparib
• Prednisone

Trial Overview The trial is examining different strengths and formulations of Niraparib and Abiraterone Acetate (AA) under modified fasted conditions to see how well the body absorbs them in men with mCRPC. The study has multiple periods to assess relative bioavailability and bioequivalence.

Participant Groups

Group I: Treatment Sequence CDB Experimental Treatment 3 Interventions

Participants will receive Treatment C in Treatment Period 1, followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Group II: Treatment Sequence CBD Experimental Treatment 3 Interventions

Participants will receive single doses of niraparib and AA using niraparib Formulation 3 as Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Group III: Treatment Sequence ADB Experimental Treatment 3 Interventions

Participants will receive Treatment A in Treatment Period 1 followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Group IV: Treatment Sequence ABD Experimental Treatment 3 Interventions

Participants will receive single doses of niraparib and abiraterone acetate (AA) using niraparib Formulation 1 as Treatment A in Treatment Period 1, followed by multiple doses of niraparib and AA using niraparib Formulation 2 as Treatment B in Treatment Period 2, followed by multiple doses of niraparib and AA using niraparib Formulation 4 as Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AA-prednisone (AAP) or AAP alone.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Niraparib at a dose of 200 mg/day was determined to be the recommended phase 2 dose when combined with abiraterone acetate plus prednisone (AAP) for patients with metastatic castration-resistant prostate cancer (mCRPC), as it showed a tolerable safety profile with no new safety signals.

The combination of niraparib with apalutamide resulted in a higher incidence of dose-limiting toxicities, leading to the decision not to further evaluate this combination, highlighting the importance of monitoring drug interactions in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). Saad, F., Chi, KN., Shore, ND., et al.[2021]

In a phase 3 trial with 1088 patients, abiraterone acetate plus prednisone significantly improved overall survival compared to placebo plus prednisone, with a median survival of 34.7 months versus 30.3 months, indicating its efficacy in treating chemotherapy-naive castration-resistant prostate cancer.

The treatment was associated with a manageable safety profile, although there were some increased risks of grade 3-4 adverse events, such as cardiac disorders and elevated liver enzymes, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Ryan, CJ., Smith, MR., Fizazi, K., et al.[2022]

In a study of 133 patients with non-metastatic castration-resistant prostate cancer, abiraterone acetate (AA) plus prednisone showed comparable overall survival and cancer-specific survival to enzalutamide (Enz) over a median follow-up of 36 months.

However, patients treated with AA plus prednisone had a significantly higher risk of non-cancer-caused death compared to those treated with Enz, suggesting that while both treatments are effective, AA plus prednisone may pose additional safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. Tsujino, T., Tokushige, S., Komura, K., et al.[2023]

Niraparib (NIRA) is an effective treatment for patients with metastatic castration-resistant prostate cancer who have specific genetic alterations, showing promising results in a Phase II study.

When combined with abiraterone acetate and prednisone, NIRA demonstrated a manageable safety profile while effectively disrupting cancer cell signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. Chi, KN., Fleshner, N., Chiuri, VE., et al.[2023]

Abiraterone acetate (AA) combined with prednisone shows favorable safety and efficacy outcomes in treating metastatic prostate cancer, particularly in patients who are asymptomatic or have mild symptoms.

The treatment is generally well tolerated, but it is important to be aware of its known toxicity profile, including mineralocorticoid and corticosteroid-related adverse events, as well as hepatotoxicity, which can inform clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A drug safety evaluation of abiraterone acetate in the treatment of prostate cancer. Castellan, P., Castellucci, R., Marchioni, M., et al.[2019]

In a study of 95 metastatic castration-resistant prostate cancer (mCRPC) patients, 52% experienced potential drug-drug interactions (DDI) with abiraterone acetate, highlighting the prevalence of polypharmacy in this population.

Patients experiencing pain and those with poorer performance status were found to be at a higher risk for these interactions, suggesting that careful medication reviews by pharmacists are essential to minimize DDI risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential drug-drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: a prevalence study in France. Bonnet, C., Boudou-Rouquette, P., Azoulay-Rutman, E., et al.[2017]

In a clinical trial involving 164 men with metastatic castration-resistant prostate cancer, abiraterone acetate combined with prednisone (5 mg twice daily) or dexamethasone (0.5 mg once daily) effectively minimized mineralocorticoid excess, which is important for patient safety.

While abiraterone with dexamethasone showed promising efficacy, it was also linked to adverse metabolic effects, such as increased insulin resistance and decreased bone mineral density, highlighting the need for careful monitoring of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study. Attard, G., Merseburger, AS., Arlt, W., et al.[2022]

In a study of 254 metastatic castration-resistant prostate cancer patients treated with abiraterone acetate plus prednisone (AA+P) over a median follow-up of 67.1 weeks, patient-reported outcomes (PROs) showed no significant decline in quality of life or cognitive function, indicating that the treatment is well-tolerated.

The study also reported a 66.4% response rate in prostate-specific antigen (PSA) levels, demonstrating the efficacy of AA+P in managing this patient population while maintaining their overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC. Gotto, G., Drachenberg, DE., Chin, J., et al.[2020]

In a phase II study involving 41 men with metastatic castration-resistant prostate cancer, increasing the dose of abiraterone acetate from 1000 mg to 2000 mg daily did not result in any significant clinical benefit, as no patients showed a prostate-specific antigen (PSA) decline of 30% or more after 12 weeks.

The study found that factors such as lower baseline circulating androgen levels and individual differences in drug metabolism may contribute to resistance against standard-dose abiraterone therapy, suggesting that simply increasing the dose is not an effective strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Friedlander, TW., Graff, JN., Zejnullahu, K., et al.[2018]

The study evaluated the effectiveness of abiraterone acetate combined with prednisone (AA+P) in 53 patients with castration-resistant prostate cancer (mCRPC), showing a good response to this treatment.

Key factors associated with higher survival rates included a longer duration of prostate cancer prior to treatment, lower pain intensity, extended treatment duration with AA+P, and favorable tumor marker levels at 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic Castration-resistant Prostate Cancer Patients With Abiraterone Acetate and Prednisone and Corresponding Survival Prognostic Factors. Jimenez Romero, ME., Gallego, MC., Navarro Serrato, JC., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). [2021]

2. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. [2022]

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

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Safety and clinical outcomes of patients treated with abiraterone acetate after docetaxel: results of the Italian Named Patient Programme. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A drug safety evaluation of abiraterone acetate in the treatment of prostate cancer. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Potential drug-drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: a prevalence study in France. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Medication patterns of abiraterone acetate plus prednisone or enzalutamide and PSA progression in veterans with metastatic castration-resistant prostate cancer. [2021]

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

Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study. [2022]

10. Canada pubmed.ncbi.nlm.nih.gov

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC. [2020]

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

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. [2018]

12. Greece pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic Castration-resistant Prostate Cancer Patients With Abiraterone Acetate and Prednisone and Corresponding Survival Prognostic Factors. [2021]