Fuzuloparib + AA-P for Prostate Cancer

Recruiting at 148 trial locations

Overseen By Chunlei Jin, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Must be taking: Androgen deprivation

Must not be taking: PARP inhibitors, CYP3A4 drugs

Disqualifiers: Brain lesions, Heart diseases, HIV, others

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 3 years

496 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether a combination of Fuzuloparib and AA-P is better for treating advanced prostate cancer. The treatment aims to kill cancer cells by preventing them from fixing their damaged DNA and by reducing hormone levels that help the cancer grow. The study includes patients with and without specific DNA repair deficiencies.

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

The trial protocol does not specify if you must stop all current medications, but you cannot use CYP3A4 inducers or inhibitors within 14 days before starting the trial.

Will I have to stop taking my current medications?

The trial requires that you have not used any CYP3A4 inducers or inhibitors within 14 days before starting the trial. If you are taking these types of medications, you may need to stop them before participating.

What data supports the idea that Fuzuloparib + AA-P for Prostate Cancer is an effective drug?

The available research shows that abiraterone acetate plus prednisone (AA+P), which is part of the Fuzuloparib + AA-P treatment, has been effective in improving survival for patients with metastatic castration-resistant prostate cancer. For example, one study reported that AA+P significantly prolonged overall survival and delayed disease progression compared to a placebo. Additionally, real-world data from Canada indicated that patients treated with AA+P had positive outcomes. While the specific combination of Fuzuloparib with AA-P is not directly covered in the provided studies, the effectiveness of AA+P suggests potential benefits when combined with Fuzuloparib. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Fuzuloparib + AA-P for Prostate Cancer?

Research shows that abiraterone acetate combined with prednisone significantly improves survival in patients with metastatic castration-resistant prostate cancer. Additionally, similar treatments like niraparib with abiraterone acetate have been studied for safety and effectiveness, suggesting potential benefits in this patient group. ^{1 2 3 4 5}

What safety data is available for the treatment Fuzuloparib + AA-P for prostate cancer?

The safety data for the treatment involving Abiraterone acetate (AA) plus prednisone (P) is well-documented. Abiraterone acetate, marketed as Zytiga, has been used in combination with prednisone to treat metastatic castration-resistant prostate cancer (mCRPC). Clinical trials and real-world studies have shown that this combination significantly improves survival and progression-free survival. The FDA approved this combination based on clinical trials demonstrating its efficacy and safety. Additionally, studies like COSMiC and REAAcT have evaluated patient-reported outcomes and tolerability, respectively, further supporting its safety profile. However, specific safety data for Fuzuloparib in combination with AA-P is not detailed in the provided research. ^{2 3 4 6 7}

Is the combination of Fuzuloparib and Abiraterone Acetate with Prednisone safe for humans?

Abiraterone acetate, often used with prednisone, has been studied in patients with prostate cancer and is generally considered safe, though it may have side effects like high blood pressure and liver function changes. Fuzuloparib's safety profile is not detailed in the provided studies, so consulting with a healthcare provider for more information is recommended. ^{2 3 4 6 7}

Is the drug combination of Abiraterone acetate, Fuzuloparib, and Prednisone promising for treating prostate cancer?

Yes, the drug combination is promising. Abiraterone acetate with Prednisone has been shown to significantly improve survival in patients with advanced prostate cancer. It helps patients live longer and delays the progression of the disease. ^{3 4 5 8 9}

What makes the drug Fuzuloparib + AA-P unique for prostate cancer?

Fuzuloparib + AA-P is unique because it combines Fuzuloparib, a PARP inhibitor (a type of drug that blocks an enzyme used by cancer cells to repair damage), with Abiraterone acetate and Prednisone, which are already known to improve survival in metastatic castration-resistant prostate cancer. This combination may offer a novel approach by targeting cancer cells in multiple ways. ^{3 4 5 8 9}

Eligibility Criteria

Men over 18 with advanced prostate cancer that's worsened despite hormone therapy can join. They must be fairly healthy, able to consent, and provide blood and tumor samples for DNA repair deficiency testing. Excluded are those with HIV, hepatitis B or C, brain tumors, heart disease, certain digestive issues or who've had prior PARP inhibitors or recent strong drug interactions.

Inclusion Criteria

I am 18 years old or older.

My organs are functioning well enough for treatment.

I have provided blood and tumor samples for DRD status testing.

Exclusion Criteria

I haven't taken any drugs that affect enzyme levels in the last 2 weeks.

My high blood pressure is not under control.

I have an active heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fuzuloparib plus AA-P or placebo plus AA-P as first-line treatment

up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 4 years

Treatment Details

Interventions

• Abiraterone acetate
• Fuzuloparib
• Fuzuloparib Placebo
• Prednisone

Trial Overview The study tests if adding Fuzuloparib to standard treatment (Abiraterone acetate and Prednisone) is better than a placebo plus the standard treatment in slowing down cancer growth. It includes two groups: one where patients' cancers have specific DNA repair issues and another without these issues.

Participant Groups

Group I: Treatment group A Experimental Treatment 1 Intervention

Fuzuloparib plus AA-P

Group II: Treatment group B Placebo Group 1 Intervention

Fuzuloparib Placebo plus AA-P

Abiraterone acetate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• High-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Jiangsu HengRui Medicine Co., Ltd.

Lead Sponsor

Trials

663

Recruited

102,000+

Founded

1970

Headquarters

Lianyungang, China

Known For

Oncology Innovations

Top Products

Camrelizumab, Rivoceranib (Apatinib)

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]

The study confirmed that the novel abiraterone acetate fine particle formulation (AAFP) at 500mg is therapeutically equivalent to the originator abiraterone acetate (OAA) at 1000mg in men with metastatic castrate-resistant prostate cancer, as both treatments resulted in comparable serum testosterone levels.

Both AAFP and OAA showed similar efficacy in reducing prostate-specific antigen (PSA) levels, with over 65% of patients in each group achieving a PSA-50 response, and no new safety concerns were identified, although musculoskeletal events were more frequent in the OAA group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase 2 therapeutic equivalence study of abiraterone acetate fine particle formulation vs. originator abiraterone acetate in patients with metastatic castration-resistant prostate cancer: The STAAR study. Stein, CA., Levin, R., Given, R., et al.[2018]

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]

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 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 100 patients with metastatic castration-resistant prostate cancer, those treated with enzalutamide (ENZA) reported significantly more fatigue and neurocognitive issues compared to those treated with abiraterone acetate plus prednisone (AA+P).

While both treatments had similar rates of severe adverse events, ENZA was associated with unique neuropsychiatric side effects such as memory impairment and confusion, indicating a need for careful monitoring of cognitive function in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT). Shore, ND., Saltzstein, D., Sieber, P., et al.[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 study of 143 men with metastatic castration-resistant prostate cancer, those treated with Enzalutamide (ENZ) experienced significantly longer biochemical progression-free survival compared to those treated with Abiraterone acetate plus Prednisone (AA+P), with a hazard ratio of 0.54.

There was no significant difference in overall survival between the two treatment groups, indicating that while ENZ may delay disease progression, it does not necessarily extend overall survival compared to AA+P.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus Prednisone/Prednisolone compared with Enzalutamide in metastatic castration resistant prostate cancer before or after chemotherapy: A retrospective study of real-world data (ACES). Das, P., Taylor, S., Price, J., et al.[2022]

In a study of 211 patients with metastatic castration-resistant prostate cancer, abiraterone acetate plus prednisone (AAP) showed significantly better outcomes than enzalutamide (ENZ) in terms of cognitive function and fatigue over the first three months of treatment.

Patients receiving AAP reported less perceived cognitive impairment and lower levels of fatigue compared to those on ENZ, indicating that AAP may be a more favorable option for managing these patient-reported outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone or enzalutamide on fatigue and cognition in patients with metastatic castration-resistant prostate cancer: initial results from the observational AQUARiUS study. Thiery-Vuillemin, A., Hvid Poulsen, M., Lagneau, E., 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. United States pubmed.ncbi.nlm.nih.gov

Randomized phase 2 therapeutic equivalence study of abiraterone acetate fine particle formulation vs. originator abiraterone acetate in patients with metastatic castration-resistant prostate cancer: The STAAR study. [2018]

3. 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]

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

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

5. 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]

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

Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT). [2021]

7. 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]

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

Abiraterone acetate plus Prednisone/Prednisolone compared with Enzalutamide in metastatic castration resistant prostate cancer before or after chemotherapy: A retrospective study of real-world data (ACES). [2022]

9. England pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone or enzalutamide on fatigue and cognition in patients with metastatic castration-resistant prostate cancer: initial results from the observational AQUARiUS study. [2021]