What side effects are associated with this type of intervention?

Common treatments for prostate cancer, including PARP inhibitors like Niraparib, often have a range of side effects. For Niraparib, these can include anemia, thrombocytopenia, and neutropenia, which are hematologic adverse events. Non-hematologic side effects may include nausea, anorexia, and asthenia. Other treatments such as androgen deprivation therapy (ADT) combined with drugs like abiraterone or enzalutamide can lead to hypertension, hypokalemia, and increased risk of fractures if osteoclast inhibitors are not used. Additionally, treatments involving docetaxel may result in febrile neutropenia. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer, including androgen receptor signaling inhibitors like enzalutamide, apalutamide, and darolutamide, which block androgen receptor pathways. Abiraterone, another approved drug, inhibits androgen production and is often used with prednisone. Additionally, the PARP inhibitor olaparib has been approved for metastatic castration-resistant prostate cancer (CRPC) with homologous recombination repair (HRR) gene mutations. These treatments aim to manage advanced stages of prostate cancer by targeting specific molecular pathways involved in cancer progression.

What other types of research exist?

Promising alternatives to Niraparib for prostate cancer patients include Olaparib and Rucaparib, both of which are PARP inhibitors. Additionally, combination therapies such as Abiraterone plus Olaparib have shown significant efficacy in clinical trials, particularly for patients with homologous recombination repair (HRR) gene defects.

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Hormone Therapy

Combination Therapy for Prostate Cancer (ASCLEPIuS Trial)

Phase 1 & 2

Waitlist Available

Led By William Jackson, M.D.

Research Sponsored by University of Michigan Rogel Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Pathologic biopsy proven adenocarcinoma of the prostate

Grade group 5

Must not have

Patients with significant cardiovascular disease potentially including severe / unstable angina, recent history of myocardial infarction, clinically significant heart failure, cerebrovascular disease, venous thromboembolic events, clinically significant arrhythmias)

Uncontrolled diabetes or known HbA1c>10

Timeline

Screening 3 weeks

Treatment Varies

Follow Up measured during the end of the 6th cycle of therapy (during week 24 +/- 7 days)

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include hormonal changes due to abiraterone and leuprolide leading to hot flashes or sexual dysfunction; digestive issues from niraparib; fatigue; skin reactions from radiotherapy; blood pressure changes due to prednisone; plus risks of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My prostate cancer was confirmed through a biopsy.

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My cancer is classified as grade group 5.

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I will use effective birth control during and for 3 months after treatment. I won't donate sperm during this time.

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My MRI shows a high chance of T3 cancer and it is grade 2 or higher.

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My cancer is classified as Grade Group 4.

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My prostate cancer is aggressive with a high PSA level and most biopsy samples are positive.

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I am 18 years old or older.

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I am fully active and can carry on all my pre-disease activities without restriction.

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My prostate cancer is aggressive, and my PSA level is 20 ng/mL or higher.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have severe heart or blood vessel problems.

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My diabetes is not under control or my HbA1c level is above 10.

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I have active hepatitis or chronic liver disease.

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I am allergic to niraparib, abiraterone acetate, leuprolide, or prednisone.

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I am not taking medications like phenytoin or rifampin.

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I have a disorder affecting my pituitary or adrenal glands.

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I have or had Crohn's disease or ulcerative colitis.

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My high blood pressure is not controlled, even with medication.

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I have a history of myelodysplastic syndrome or leukemia.

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I have not had major surgery in the last month.

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I have had treatment for prostate cancer before.

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I have severe depression.

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My tests show a high chance of advanced cancer.

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My scans show cancer has spread to distant parts of my body.

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My prostate is larger than 80 cc as measured by imaging.

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I haven't taken certain cancer or hormone treatments in the last 3 months.

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I have a digestive condition that affects how my body absorbs food.

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I have had radiation therapy in the pelvic area before.

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I do not have any infections or conditions that prevent me from taking prednisone.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ measured during the end of the 6th cycle of therapy (during week 24 +/- 7 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~measured during the end of the 6th cycle of therapy (during week 24 +/- 7 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and measured during the end of the 6th cycle of therapy (during week 24 +/- 7 days) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting toxicities (Phase 1)

Proportion of patients experiencing biochemical failure

Secondary study objectives

Change in health related quality of life

Overall survival

Proportion of patients with distant metastases

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Niraparid Dose EscalationExperimental Treatment4 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Leuprolide

2008

Completed Phase 4

~19040

Stereotactic body radiotherapy (SBRT)

2018

Completed Phase 1

~80

Niraparib

2018

Completed Phase 4

~2400

Abiraterone Acetate

2015

Completed Phase 4

~1880

0 / 28Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target the androgen receptor signaling pathway, which is crucial for the growth and survival of prostate cancer cells. Androgen deprivation therapy (ADT) reduces androgen levels, thereby limiting the stimulation of prostate cancer cells. Androgen receptor inhibitors, such as enzalutamide and apalutamide, block the androgen receptor, preventing androgens from promoting cancer cell growth. PARP inhibitors like Niraparib target cancer cells with deficiencies in DNA repair mechanisms, such as those with BRCA1/2 mutations, by inhibiting the PARP enzyme, leading to cancer cell death. These treatments are vital as they exploit specific vulnerabilities in prostate cancer cells, offering targeted and effective therapeutic options.