Combination Therapy for Prostate Cancer

(ASCLEPIuS Trial)

Not currently recruiting at 5 trial locations

Overseen By UM Cancer AnswerLine

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Anti-androgens, Chemotherapy, Immunotherapy, others

Disqualifiers: Metastatic disease, T4 disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for prostate cancer. Researchers aim to determine the safest dose of niraparib (also known as Zejula) when combined with other treatments, such as radiotherapy and hormone therapy, and to evaluate the effectiveness of this approach over three years. Men with biopsy-confirmed prostate cancer who meet specific criteria, such as certain imaging test levels or specific biopsy results, may qualify for this study. As a Phase 1/Phase 2 trial, the study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. Specifically, you must stop taking non-steroidal anti-androgens, steroidal antiandrogens, oral ketoconazole, chemotherapy, immunotherapy, estrogens, and radiopharmaceuticals 3 months before joining the study. Additionally, spironolactone and other investigational drug therapies are prohibited 30 days before starting the study treatment.

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

Research has shown that combining niraparib with other treatments like abiraterone acetate is generally safe for prostate cancer patients. Studies have found that this combination has an expected safety profile, with no new safety concerns. However, some patients experienced side effects such as low red blood cell count (anemia) and low white blood cell count (neutropenia).

Stereotactic Body Radiotherapy (SBRT) uses precise radiation to target cancer cells, minimizing harm to nearby tissues. It is commonly used and usually well-tolerated. While it can cause tiredness and skin irritation, these effects are typically mild.

In summary, these treatments have been researched and are considered to have a manageable safety profile. However, like all treatments, they can have side effects, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine innovative approaches to attack the cancer more effectively. Niraparib, a PARP inhibitor, is used to target cancer cells with specific DNA repair weaknesses, offering a different mechanism than traditional hormone therapies like Leuprolide. Additionally, by integrating Stereotactic Body Radiotherapy (SBRT), which delivers precise high-dose radiation, the treatment aims to minimize damage to surrounding healthy tissues. This combination strategy holds promise for enhanced effectiveness and potentially fewer side effects compared to standard treatments like Abiraterone Acetate and Leuprolide alone.

What evidence suggests that this combination therapy could be effective for prostate cancer?

This trial will explore the use of Niraparib in combination with Stereotactic Body Radiotherapy (SBRT) for prostate cancer. Studies have shown that combining Niraparib with Abiraterone Acetate and Prednisone may effectively treat prostate cancer. Research indicates that this combination can reduce the risk of cancer progression by 37% in some patients. Specifically, another study found that this treatment significantly extended the time patients lived without disease progression compared to standard treatments. While researchers continue to collect more data, early results are encouraging for this treatment approach. ^{2 4 6 7 8}

Who Is on the Research Team?

William Jackson, M.D.

Principal Investigator

University of Michigan Rogel Cancer Center

Daniel Spratt, M.D.

Principal Investigator

Case Western Reserve University - Seidman Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer, who haven't had prior treatments like radiation or anti-androgen therapy. They must have a specific grade of cancer severity, adequate organ function, and agree to use effective contraception. Exclusions include those with other recent cancers, certain heart conditions, uncontrolled diabetes or hypertension, large prostate size (>80 cc), and allergies to the trial drugs.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent

My organs and bone marrow are working well.

My prostate cancer was confirmed through a biopsy.

Exclusion Criteria

Lack of tissue from biopsy to be sent for correlative studies

My doctor has noted a significant enlargement of my prostate's median lobe.

I do not have severe heart or blood vessel problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Establish the maximum tolerable dose of niraparib when combined with prostate stereotactic body radiotherapy (SBRT), abiraterone, leuprolide, and prednisone

16 weeks

Treatment

Participants receive niraparib, abiraterone, leuprolide, prednisone, and SBRT

24 weeks

Regular visits for monitoring and treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Leuprolide
• Niraparib
• Stereotactic Body Radiotherapy (SBRT)

Trial Overview The study is testing the highest dose of niraparib (a PARP inhibitor) that's safe when combined with SBRT (targeted radiotherapy), abiraterone (hormone therapy), leuprolide (hormone therapy), and prednisone in men with prostate cancer. It also aims to see how well this combination prevents cancer from returning within three years.

How Is the Trial Designed?

Group I: Niraparid Dose Escalation Experimental Treatment 4 Interventions

Dose Level 1: 100 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT Dose Level 2: 200 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT Dose Level 3: 200 mg PO daily of Niraparib without breaks during SBRT until completion of 6 cycles.

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?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Stereotactic body radiotherapy (SBRT) shows a high local control rate of 98.1% in treating oligorecurrent prostate cancer limited to lymph nodes, based on a systematic review of 363 patients across nine studies with a median follow-up of 19.23 months.

The treatment demonstrated a low incidence of toxicity, with only 5.6% of patients experiencing grade ≥2 adverse effects, and no cases of grade 4 toxicity, suggesting that SBRT is a safe option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring All Avenues for Radiotherapy in Oligorecurrent Prostate Cancer Disease Limited to Lymph Nodes: A Systematic Review of the Role of Stereotactic Body Radiotherapy. Ponti, E., Lancia, A., Ost, P., et al.[2022]

In a phase I/II clinical trial involving 91 prostate cancer patients, stereotactic body radiation therapy (SBRT) demonstrated excellent long-term efficacy, with a 98.6% freedom from biochemical failure at 5 years and 100% distant metastasis-free survival.

While SBRT was effective, higher doses (greater than 47.5 Gy) were associated with increased severe late toxicity, highlighting the need for careful dose management to minimize adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for low and intermediate risk prostate cancer-Results from a multi-institutional clinical trial. Hannan, R., Tumati, V., Xie, XJ., 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 study involving 344 high-risk prostate cancer patients with a median follow-up of 49.5 months, stereotactic body radiation therapy (SBRT) demonstrated a high 4-year biochemical recurrence-free survival rate of 81.7% and distant metastasis-free survival rate of 89.1%.

The treatment showed a favorable safety profile, with low incidences of late grade ≥3 genitourinary (2.3%) and gastrointestinal (0.9%) toxicities, indicating that SBRT is both effective and safe for high-risk prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients. van Dams, R., Jiang, NY., Fuller, DB., et al.[2022]

In a study of 17 men with oligometastatic prostate cancer treated with stereotactic body radiation therapy (SBRT), local control was achieved in 100% of cases, and over half of the patients (53%) had an undetectable prostate-specific antigen (PSA) after treatment.

The treatment was well-tolerated, with only mild toxicities reported and no severe side effects (grade ≥3), indicating that SBRT is a safe and effective option for managing oligometastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy in the treatment of oligometastatic prostate cancer. Ahmed, KA., Barney, BM., Davis, BJ., et al.[2022]

In a study of 43 patients with oligometastatic prostate cancer treated with stereotactic body radiation therapy (SBRT), 67.4% showed a positive prostate-specific antigen (PSA) response, leading to a median androgen deprivation therapy-free survival (ADT-FS) of 15.6 months.

Patients treated with SBRT had a significantly longer ADT-FS compared to a control group, with 17.3 months versus 4.19 months, and experienced no severe adverse events, highlighting SBRT's safety and efficacy in delaying the need for hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of Using Stereotactic Body Radiotherapy in Patients With Metachronous Oligometastases of Hormone-Sensitive Prostate Cancer Detected by [18F]fluoromethylcholine PET/CT. Bouman-Wammes, EW., van Dodewaard-De Jong, JM., Dahele, M., et al.[2022]

Intratumoral androgen biosynthesis is crucial in the development of metastatic castration-resistant prostate cancer (mCRPC), suggesting that these tumors continue to rely on androgens for growth even after androgen deprivation therapy.

A novel metabolite of abiraterone, D4A, shows strong antitumor effects by inhibiting androgen biosynthesis and blocking the androgen receptor, indicating its potential as a new treatment option for mCRPC, especially in cases resistant to existing therapies like enzalutamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances in intratumoral androgen metabolism in castration-resistant prostate cancer. Penning, TM., Tamae, D.[2018]

Stereotactic body radiotherapy (SBRT) is effective for treating localized and metastatic prostate cancer, as prostate cancer shows increased sensitivity to higher radiation doses due to its low α/β ratio.

There is potential for combining SBRT with systemic therapies like androgen deprivation therapy (ADT) and immunotherapy, as SBRT may enhance immune responses, making it a promising area for ongoing research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. Adorno Febles, VR., Blacksburg, S., Haas, JA., et al.[2020]

Citations

1. nature.com nature.com/articles/s41591-025-03961-8

Niraparib and abiraterone acetate plus prednisone for ... The data for overall survival, a key secondary endpoint, are immature (193/389 events) but favor niraparib (hazard ratio = 0.79 (95% confidence ...

2. urologytimes.com urologytimes.com/view/published-data-show-benefit-of-niraparib-with-aap-in-hrr-deficient-mcspc

Published data show benefit of niraparib with AAP in HRR- ... At a median follow-up of 30.8 months, data showed that the addition of niraparib led to a 37% reduction in the risk of radiographic progression ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9361481/

Niraparib in patients with metastatic castration-resistant ... Here, we report the final efficacy and safety results of a multicentre, open-label, phase 2 study of niraparib in patients with mCRPC and tumour DRD whose ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01649

Niraparib and Abiraterone Acetate for Metastatic Castration ... Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.

5. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-prostate-cancer/161080-asco-2025-phase-3-amplitude-trial-niraparib-and-abiraterone-acetate-plus-prednisone-for-metastatic-castration-sensitive-prostate-cancer-patients-with-alterations-in-homologous-recombination-repair-genes.html

ASCO 2025: Phase 3 AMPLITUDE Trial: Niraparib and ... The AMPLITUDE trial is a randomized, double-blind, placebo-controlled phase 3 study evaluating the efficacy of a fixed daily tablet of niraparib (200 mg)

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12276826/

FDA Approval Summary: Niraparib Plus Abiraterone Acetate ... FDA Approval Summary: Niraparib Plus Abiraterone Acetate Fixed Dose Combination for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02854436

NCT02854436 | An Efficacy and Safety Study of Niraparib ... The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of niraparib in men with metastatic castration-resistant prostate cancer ( ...

8. journals.lww.com journals.lww.com/atmr/fulltext/2024/07000/safety_and_efficacy_of_niraparib_in_metastatic.8.aspx

Safety and Efficacy of Niraparib in Metastatic Castration-re... Niraparib has been found to have a positive impact on rPFS, TSP and TCC, but it has also been associated with some adverse events, such as anaemia, neutropenia ...