Niraparib + Abiraterone Acetate + Prednisone for Metastatic Prostate Cancer

(MAGNITUDE Trial)

Recruiting at 410 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: GnRHa

Must not be taking: PARP inhibitors, AR-targeted therapy

Disqualifiers: Brain metastases, MDS/AML, other malignancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 32 months

765 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate plus prednisone (AAP) compared to AAP and placebo.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have had certain treatments like PARP inhibitors or specific therapies for metastatic prostate cancer. It's best to discuss your current medications with the trial team.

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

Research shows that Abiraterone Acetate combined with Prednisone significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer. This suggests that the combination of these drugs could be effective in treating metastatic prostate cancer. ^{1 2 3 4 5}

Is the combination of Niraparib, Abiraterone Acetate, and Prednisone safe for humans?

Abiraterone acetate combined with prednisone is generally considered safe for treating metastatic prostate cancer, but it can cause side effects like low potassium levels, high blood pressure, fluid retention, heart issues, and liver problems. Niraparib has been studied for safety in combination with abiraterone acetate and prednisone, but specific safety details for this combination are not provided in the available research. ^{2 6 7 8 9}

What makes the drug combination of Niraparib, Abiraterone Acetate, and Prednisone unique for treating metastatic prostate cancer?

This drug combination is unique because it includes Niraparib, a PARP inhibitor (a type of drug that blocks an enzyme used by cancer cells to repair damage), alongside Abiraterone Acetate and Prednisone, which are already used to treat metastatic castration-resistant prostate cancer. The addition of Niraparib may offer a novel approach by potentially enhancing the effectiveness of the existing treatment regimen. ^{1 2 3 5 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for men with metastatic prostate cancer who have specific genetic changes (HRR gene alteration), haven't had certain cancers or treatments like PARP inhibitors, and are on hormone therapy to keep testosterone low. They should not have symptomatic brain tumors or blood disorders like MDS/AML.

Inclusion Criteria

My prostate cancer has spread, and my testosterone is very low due to treatment or surgery.

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

My cancer has a positive HRR gene alteration.

Exclusion Criteria

I have had specific prostate cancer treatments before joining this study.

I have or had myelodysplastic syndrome or acute myeloid leukemia.

I have brain metastases that are causing symptoms.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib in combination with abiraterone acetate and prednisone or placebo for metastatic prostate cancer

Up to 32 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension

Participants may continue to receive open-label combination of niraparib and abiraterone acetate plus prednisone, or cross over to this treatment if initially on placebo

Treatment Details

Interventions

• Abiraterone Acetate
• Niraparib
• Placebo
• Prednisone

Trial Overview The study tests the effectiveness of Niraparib combined with Abiraterone Acetate and Prednisone against just Abiraterone Acetate and Prednisone in treating metastatic prostate cancer. Participants will be randomly assigned to either receive the combination treatment or the standard treatment plus a placebo.

Participant Groups

Group I: Cohort 3 (Open-label): Participants with mCRPC Experimental Treatment 2 Interventions

Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg.

Group II: Cohort 2: Participants with mCRPC and No HRR Gene Alteration Experimental Treatment 4 Interventions

Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg. In the OLE phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.

Group III: Cohort 1: Participants with mCRPC and HRR Gene Alteration Experimental Treatment 4 Interventions

Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg. In the open label extension (OLE) phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.

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?

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

In a phase 3 trial involving 1199 patients, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly improved overall survival, with a median survival not reached in the abiraterone group compared to 34.7 months in the placebo group.

The study also showed that patients receiving abiraterone had a median radiographic progression-free survival of 33.0 months, compared to 14.8 months in the placebo group, indicating a strong benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi, K., Tran, N., Fein, L., et al.[2022]

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 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 1199 men with metastatic castration-sensitive prostate cancer, treatment with abiraterone acetate plus prednisone (AA+P) significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) compared to placebo, particularly in patients with lung metastases.

Patients with visceral metastases (VM) who received AA+P had a median OS of 55.4 months versus 33.0 months for those on placebo, and a median rPFS of 30.7 months compared to 18.3 months, indicating that AA+P is an effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: A post-hoc exploratory analysis of the LATITUDE study. Baciarello, G., Özgüroğlu, M., Mundle, S., 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]

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]

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]

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 study involving 202 patients with metastatic castration-resistant prostate cancer, the sequence of treatment with abiraterone acetate followed by enzalutamide resulted in a longer time to second PSA progression (19.3 months) compared to the reverse sequence (15.2 months), indicating a more effective treatment strategy.

Enzalutamide demonstrated a significantly higher PSA response rate (36%) as a second-line therapy compared to abiraterone (4%), suggesting that enzalutamide is more effective when used after abiraterone in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Khalaf, DJ., Annala, M., Taavitsainen, S., et al.[2021]

References

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

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022]

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

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

3. 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]

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

Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: A post-hoc exploratory analysis of the LATITUDE study. [2022]

5. 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]

6. 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]

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

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

8. 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]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. [2021]