Niraparib + Abiraterone Acetate and Prednisone for Prostate Cancer

(AMPLITUDE Trial)

Recruiting at 513 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Androgen deprivation therapy

Must not be taking: PARP inhibitors, Long-term corticosteroids

Disqualifiers: Adrenal dysfunction, MDS/AML, 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 47 months

696 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to determine if the combination of niraparib with Abiraterone Acetate (AA) plus prednisone compared with AA plus prednisone in participants with deleterious germline or somatic Homologous Recombination Repair (HRR) gene-mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) provides superior efficacy in improving radiographic progression-free survival (rPFS).

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, you must continue androgen deprivation therapy (ADT) and cannot use long-term systemic corticosteroids during the study.

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

Research shows that Abiraterone Acetate combined with Prednisone significantly improves survival and delays disease progression in men with metastatic castration-resistant prostate cancer. This suggests that the combination with Niraparib may also be effective, although specific data on this exact combination is not provided. ^{1 2 3 4 5}

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

Abiraterone acetate combined with prednisone has been shown to be generally well tolerated in patients with prostate cancer, with known side effects including issues related to mineralocorticoids (hormones that help control blood pressure and the balance of fluids and electrolytes) and liver toxicity. Understanding these side effects can help in making informed decisions about treatment. ^{1 2 3 6 7}

How is the drug combination of Niraparib, Abiraterone Acetate, and Prednisone unique for prostate cancer?

This drug combination is unique because it includes Niraparib, which is not typically used in standard prostate cancer treatments. Niraparib is a PARP inhibitor (a type of drug that blocks certain enzymes involved in repairing damaged DNA), potentially offering a novel mechanism of action when combined with Abiraterone Acetate and Prednisone, which are already used to treat prostate cancer. ^{1 4 5 8 9}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Men with prostate cancer that has spread and is sensitive to hormone therapy can join if they have specific gene changes related to DNA repair. They must have started hormone treatment at least two weeks before joining, but not had extensive prior treatments like radiation or certain drugs.

Inclusion Criteria

I started hormone therapy for my cancer more than 14 days ago and am willing to continue it.

I have prostate cancer and have had limited prior treatments for it.

My cancer has spread, confirmed by scans.

Exclusion Criteria

I am not on long-term steroids higher than 5mg of prednisone or equivalent.

I have been treated with a PARP inhibitor before.

I have or had myelodysplastic syndrome or acute myeloid leukemia.

Timeline

Prescreening

Biomarker evaluation for eligibility only

2-4 weeks

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib with abiraterone acetate plus prednisone or placebo with abiraterone acetate plus prednisone in 28-day cycles

Up to 47 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 78 months

Treatment Details

Interventions

• Abiraterone acetate (AA)
• Niraparib
• Prednisone

Trial Overview The trial tests if adding Niraparib (a drug for DNA repair defects) to Abiraterone Acetate and Prednisone improves outcomes in men whose prostate cancer has spread. Participants are randomly assigned to either the combination treatment or just AA plus prednisone.

Participant Groups

Group I: Niraparib with Abiraterone Acetate plus Prednisone (AAP) Experimental Treatment 3 Interventions

Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg), abiraterone acetate (AA) 1000 mg plus prednisone 5 mg once daily.

Group II: AA plus Prednisone (AAP) Active Control 3 Interventions

Participants will receive the following in each 28-day treatment cycle: matching placebo for Niraparib along with AA 1000 mg plus prednisone 5 mg once daily.

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 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]

In a study of 148 patients with metastatic castration-resistant prostate cancer, maintaining abiraterone acetate plus prednisone (AAP) during docetaxel treatment did not improve radiographic progression-free survival compared to docetaxel plus prednisone alone, with rates of 34.9% and 33.9% respectively after 12 months.

The combination of docetaxel and AAP resulted in significantly higher rates of severe neutropenia (59.6%) compared to docetaxel plus prednisone (27.7%), suggesting that continuing AAP may increase treatment-related risks without providing additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II randomised trial of abiraterone acetate plus prednisone in combination with docetaxel or docetaxel plus prednisone after disease progression to abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer: The ABIDO-SOGUG trial. Climent, MA., Font, A., Durán, I., 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 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]

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 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 1088 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate combined with prednisone significantly improved radiographic progression-free survival (rPFS) compared to prednisone alone, with a median rPFS of 16.5 months versus 8.2 months.

Abiraterone acetate also showed a trend towards improved overall survival (OS) with a median of 35.3 months compared to 30.1 months for prednisone, indicating a potential benefit in prolonging life, while maintaining a favorable safety profile over long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Rathkopf, DE., Smith, MR., de Bono, JS., et al.[2022]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

A phase II randomised trial of abiraterone acetate plus prednisone in combination with docetaxel or docetaxel plus prednisone after disease progression to abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer: The ABIDO-SOGUG trial. [2022]

4. 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]

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

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

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

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

7. 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]

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). [2022]