Fuzuloparib + AA-P for Prostate Cancer

Not currently recruiting at 183 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for advanced prostate cancer that has spread despite other treatments. Researchers aim to determine if adding Fuzuloparib (an experimental treatment) to the usual treatment of AA-P (Abiraterone acetate and Prednisone) delays cancer progression. Participants are divided into two groups: one receives the new treatment, and the other receives a placebo (a substance with no active medicine) added to AA-P. Men whose prostate cancer has worsened during hormone therapy might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Fuzuloparib, when combined with treatments like abiraterone, is generally safe for patients. In studies, most side effects were manageable, though some patients experienced low red blood cell counts, low potassium levels, and liver issues. Therefore, patients and doctors should regularly monitor blood counts and liver function.

Patients who previously used the combination of Fuzuloparib and abiraterone generally tolerated it well. Although some experienced more serious side effects, these were uncommon. Participants should discuss potential risks and benefits with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about Fuzuloparib for prostate cancer because it offers a unique approach by combining a PARP inhibitor, Fuzuloparib, with the standard hormone therapy Abiraterone acetate plus Prednisone (AA-P). Unlike traditional treatments that primarily target hormone pathways, Fuzuloparib specifically targets and disrupts cancer cell DNA repair mechanisms, potentially enhancing the effectiveness of hormone therapy. This combination could lead to improved outcomes for patients, particularly those whose cancer has become resistant to existing hormone treatments. By tackling the cancer cells from a different angle, this treatment has the potential to provide new hope for patients with advanced prostate cancer.

What evidence suggests that Fuzuloparib plus AA-P might be an effective treatment for prostate cancer?

Research has shown that Fuzuloparib, when combined with abiraterone acetate (AA), may help treat prostate cancer. One study demonstrated a significant drop in prostate-specific antigen (PSA) levels, with over 79% of patients seeing their PSA levels reduced by more than half, and 61.5% experiencing a reduction of over 90%. Another study found a high rate of complete and minimal remaining cancer responses, indicating strong potential effectiveness. In this trial, participants in Treatment Group A will receive Fuzuloparib plus AA-P, while those in Treatment Group B will receive a placebo instead of Fuzuloparib, alongside AA-P. These findings suggest that Fuzuloparib could be a powerful addition to current prostate cancer treatments. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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

My organs are functioning well enough for treatment.

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

Able and willing to provide a written informed consent

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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)

Published Research Related to This Trial

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]

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 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]

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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7369176/

Phase I dose-escalation and expansion study of PARP ... Among patients treated with fluzoparib ≥120 mg/d, median progression-free survival (mPFS) was 7.2 [95% confidence interval (95% CI), 1.8−9.3] months in OC, 9.3 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666379125000916

Article Neoadjuvant fuzuloparib combined with abiraterone ... The combined pCR/MRD rate is 46% (95% confidence interval [CI]: 29%–63%), with a 53% 2-year biochemical progression-free survival rate. Grade ≥3 ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03225-3/fulltext

1625P Fuzuloparib combined with abiraterone in the ... Three patients achieved pCR, and 13 achieved MRD, resulting in a pCR/MRD rate of 45.7% (95%CI: 28.8%-63.4%) in the intention-to-treat population. Median ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03250-2/fulltext

1650P Fuzuloparib plus abiraterone acetate and ... The maximum reduction in PSA exceeded 50% for 31 (79.5%) pts and 90% for 24 (61.5%) pts. ORR was 60% in pts with measurable lesions.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04691804

Study Details | NCT04691804 | A Multicenter, Randomized, ... To evaluate whether Fuzuloparib plus AA-P is superior to placebo plus AA-P as first-line treatment by assessment of radiographic progression-free survival (rPFS) ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.356

Results from multicenter, phase 2 FAST-PC trial. The combined regimen is generally safe and reliable, while special vigilance should be paid to the occurrence of anemia, hypokalemia and liver dysfunction.