Combination Therapy for Prostate Cancer

(ASCLEPIuS Trial)

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

102 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new combination treatment for prostate cancer. It includes a cancer drug, precise radiation, and three other medications. The goal is to find the best dose and see if it can prevent cancer from coming back over time. Docetaxel is currently the standard treatment for hormone-refractory prostate cancer.

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.

What data supports the effectiveness of the treatment Stereotactic Body Radiotherapy (SBRT) for prostate cancer?

Research shows that Stereotactic Body Radiotherapy (SBRT) is effective for treating both localized and metastatic prostate cancer, with evidence suggesting it may enhance the immune response and work well in combination with other therapies. ^{1 2 3 4 5}

Is the combination therapy for prostate cancer safe for humans?

Stereotactic body radiation therapy (SBRT) for prostate cancer is generally considered safe, with studies indicating it does not cause major side effects and maintains quality of life. ^{1 2 4 6 7}

How is the combination treatment for prostate cancer unique?

This combination treatment is unique because it combines multiple approaches: Abiraterone Acetate, which blocks a key enzyme to reduce hormone levels that fuel cancer growth; Leuprolide, which lowers testosterone levels; Niraparib, a PARP inhibitor that helps prevent cancer cells from repairing themselves; and Stereotactic Body Radiotherapy (SBRT), a precise form of radiation therapy. This multi-faceted approach targets prostate cancer from different angles, potentially improving outcomes compared to single treatments. ^{2 5 8 9 10}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

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]

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]

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 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 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]

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]

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]

References

1. Netherlands 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. [2022]

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

Stereotactic body radiation therapy for low and intermediate risk prostate cancer-Results from a multi-institutional clinical trial. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy in the treatment of oligometastatic prostate cancer. [2022]

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

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy as treatment for organ confined low- and intermediate-risk prostate carcinoma, a 7-year study. [2022]

7. United States 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. [2022]

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

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

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

Current advances in intratumoral androgen metabolism in castration-resistant prostate cancer. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Patient-Reported Financial Burden Following Stereotactic Body Radiation Therapy for Localized Prostate Cancer. [2022]