CJNJ-67652000 + Prednisone for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: LHRH analogs

Must not be taking: PARP inhibitors

Disqualifiers: Myelodysplastic syndrome, HIV, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well abiraterone acetate/niraparib (CJNJ-67652000 \[niraparib/abiraterone acetate fixed-dose combination\]) and prednisone works in treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and who have a mutation in the SPOP gene. CJNJ-67652000 (niraparib/abiraterone acetate fixed-dose combination) is a drug which stops certain cancer cells from being able to repair themselves from damage, leading to the death of the cancer cell. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving CJNJ-67652000 and prednisone may kill more tumor cells in patients with metastatic prostate cancer than giving these drugs alone.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain antiretroviral therapies or medications that might interfere with the study drug, you may need to consult with the trial sponsor. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination CJNJ-67652000 + Prednisone for prostate cancer?

Research shows that combining niraparib with abiraterone acetate and prednisone has shown promising results in patients with metastatic castration-resistant prostate cancer, especially those with specific genetic alterations, by improving outcomes and having a manageable safety profile. ^{1 2 3 4 5}

Is the combination of Niraparib and Prednisone safe for humans?

The combination of Niraparib with Prednisone has been studied in patients with metastatic castration-resistant prostate cancer, showing a manageable safety profile, meaning that while there may be side effects, they are generally considered acceptable and can be managed. ^{1 2 4 5 6}

What makes the drug CJNJ-67652000 + Prednisone for prostate cancer unique?

This treatment combines Niraparib, a drug that blocks proteins involved in DNA repair, with prednisone, a steroid, to target prostate cancer that has become resistant to standard hormone therapies. It is particularly aimed at patients with specific genetic changes and has shown promising results in those who have already tried other treatments. ^{1 5 6 7 8}

Research Team

Daniel S. Childs, MD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

Men aged 18+ with advanced prostate cancer resistant to castration and spread beyond the original site, having specific SPOP gene mutations. They can have had one prior chemotherapy but must be in relatively good health (ECOG status 0-2) with adequate blood counts and organ function. Men must agree not to donate sperm and use contraception during the trial.

Inclusion Criteria

My cancer has a specific SPOP mutation.

Committed to specific measures during and after the study period

I have had only one prior treatment with taxane chemotherapy.

Exclusion Criteria

I have brain metastases that are causing symptoms.

I do not have any unmanaged ongoing illnesses.

Poor prognosis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CJNJ-67652000 and prednisone orally. Blood specimen collection, CT or MRI, and bone scans are conducted throughout the trial.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and progression-free survival.

Up to 30 days after last treatment dose

Treatment Details

Interventions

• Niraparib
• Prednisone

Trial Overview The effectiveness of CJNJ-67652000 (a combination of niraparib/abiraterone acetate) alongside prednisone is being tested for treating metastatic castration-resistant prostate cancer with SPOP mutations. The study will assess if this drug combo kills more tumor cells compared to standard treatments.

Participant Groups

Group I: Treatment (CJNJ-67652000 and prednisone) Experimental Treatment 6 Interventions

Patients receive CJNJ-67652000 PO and prednisone PO on study. Patients also undergo blood specimen collection, CT or MRI, and bone scan throughout the trial.

Niraparib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Zejula for:

• Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
• Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy

Approved in United States as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status

Approved in Canada as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

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]

In the MAGNITUDE study, patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 alterations showed significant improvement in radiographic progression-free survival (rPFS) when treated with niraparib plus abiraterone acetate and prednisone, with a median rPFS of 19.5 months compared to 10.9 months for the placebo group.

The study, which included 212 patients with homologous recombination repair gene alterations, found no new safety concerns with the treatment, highlighting the efficacy and safety of niraparib plus AAP for this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Chi, KN., Sandhu, S., Smith, MR., et al.[2023]

In a study of 1,050 patients with metastatic castration-resistant prostate cancer, adding bevacizumab to standard docetaxel and prednisone therapy improved progression-free survival (PFS) and objective response rates, but did not significantly enhance overall survival (OS).

The combination treatment with bevacizumab resulted in higher rates of severe treatment-related toxicity and treatment-related deaths compared to standard therapy alone, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. Kelly, WK., Halabi, S., Carducci, M., et al.[2022]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

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 combination of niraparib, a PARP inhibitor, with Radium-223 was found to be safe for treating metastatic castrate-resistant prostate cancer (mCRPC) in men without known BRCA mutations, with manageable dose-limiting toxicities (DLTs) primarily related to blood cell counts.

In a study of 30 patients, the maximum tolerated dose (MTD) varied based on prior chemotherapy exposure, indicating that personalized dosing may be necessary; further research is needed to explore biomarkers that could predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. Quinn, Z., Leiby, B., Sonpavde, G., et al.[2023]

In a phase III study involving 793 participants with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), the combination of pembrolizumab and olaparib did not significantly improve radiographic progression-free survival (rPFS) or overall survival (OS) compared to next-generation hormonal agents (NHA).

Although the combination therapy showed a higher objective response rate (16.8% vs. 5.9% for NHA), the study was ultimately stopped for futility, indicating that it did not provide a meaningful benefit in prolonging survival or delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. Antonarakis, ES., Park, SH., Goh, JC., et al.[2023]

Chronic treatment with the broad-spectrum AR antagonist JNJ-pan-AR can lead to resistance in prostate cancer cells, with specific enzymes like AKR1C3 identified as key drivers of this resistance.

Targeting AKR1C3 may enhance the effectiveness of antiandrogens and help prevent disease progression in castration-resistant prostate cancer (CRPC), suggesting a potential new therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AKR1C3 mediates pan-AR antagonist resistance in castration-resistant prostate cancer. Hertzog, JR., Zhang, Z., Bignan, G., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. [2023]

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

Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. [2019]

5. 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]

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

Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. [2023]

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

Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. [2023]

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

AKR1C3 mediates pan-AR antagonist resistance in castration-resistant prostate cancer. [2021]