A Multi-Center Trial of Androgen Suppression With Abiraterone Acetate, Leuprolide, PARP Inhibition and Stereotactic Body Radiotherapy in Prostate Cancer

NCT ID: NCT04194554

Last Updated: 2025-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-06

Study Completion Date

2027-05-31

Brief Summary

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The purpose of this study is to establish the maximum tolerable dose of niraparib when combined with prostate stereotactic body radiotherapy (SBRT), abiraterone, leuprolide, and prednisone (the phase 1 portion of the study) and determine 3-year biochemical PSA recurrence free-survival with this treatment approach (the phase 2 portion of the study).

Detailed Description

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Conditions

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Prostate Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Time to Event Continual Reassessment Method (TITE-CRM) dose-finding clinical trial design.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Niraparid Dose Escalation

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.

Group Type EXPERIMENTAL

Niraparib

Intervention Type DRUG

given PO per dose escalation schedule

Leuprolide

Intervention Type DRUG

22.5 mg q3 month

Abiraterone Acetate

Intervention Type DRUG

1000 mg daily

Stereotactic body radiotherapy (SBRT)

Intervention Type RADIATION

5-6 fraction SBRT (total dose: 37.5-40 Gy)

Interventions

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Niraparib

given PO per dose escalation schedule

Intervention Type DRUG

Leuprolide

22.5 mg q3 month

Intervention Type DRUG

Abiraterone Acetate

1000 mg daily

Intervention Type DRUG

Stereotactic body radiotherapy (SBRT)

5-6 fraction SBRT (total dose: 37.5-40 Gy)

Intervention Type RADIATION

Other Intervention Names

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Ultra-hypofractionated radiotherapy

Eligibility Criteria

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Inclusion Criteria

1. Pathologic biopsy proven adenocarcinoma of the prostate
2. At least one of the following criteria:

* cN1 on conventional or PET imaging
* Grade group 5
* Grade group 4
* Grade group 3 and PSA ≥20 ng/mL
* High probability of Radiographic T3 on MRI AND Grade group ≥2
* Grade Group 3 AND PSA ≥10 ng/mL AND ≥50% positive biopsy cores
3. Age ≥ 18
4. ECOG \< 1
5. Adequate organ and marrow function as defined per protocol.
6. Use of highly effective contraception (e.g. condoms) for the duration of treatment and a minimum of 120 days thereafter. Men must also agree not to donate sperm for the duration of the study participation, and for at least 120 days thereafter.
7. International Prostate Symptoms Score (IPSS) ≤ 20
8. Medically fit for treatment and agreeable to follow-up
9. Ability to understand and the willingness to sign a written informed consent
10. Tissue available for MiOncoSeq testing to assign DNA repair deficiency status

Exclusion Criteria

1. Clinical or radiographic evidence of distant metastatic disease by CT/bone scan
2. Clinical or radiographic evidence of high probability of clinical T4 disease
3. Prostate gland size \>80 cc measured by ultrasound or MRI
4. Prominent median lobe assessed by treating physician
5. Lack of tissue from biopsy to be sent for correlative studies
6. Any prior treatment for prostate cancer (incudes history of TURP within 5 years of enrollment, chemotherapy, radiation therapy, or anti-androgen therapy)
7. Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies.
8. Prohibited 3 months before participant registration and during administration of study treatment: non-steroidal anti-androgens (e.g., bicalutamide, flutamide, nilutamide), steroidal antiandrogens (megestrol acetate, cyproterone acetate), oral ketoconazole, chemotherapy, immunotherapy, estrogens, radiopharmaceuticals.
9. History of prior pelvic radiation therapy
10. Concurrent treatment with strong CYP3A4 inducers such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital
11. Enrollment concurrently in another investigational drug study within 1 month of registration
12. History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer
13. History of or active Crohn's disease or ulcerative colitis
14. Contraindication to or inability to tolerate MRIs
15. Patients with severe depression
16. Uncontrolled diabetes or known HbA1c\>10
17. Any gastrointestinal disorder affecting absorption
18. Active pituitary or adrenal dysfunction
19. 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)
20. Uncontrolled hypertension with persistently elevated systolic blood pressure \>160 mmgHg or diastolic blood pressure \>100 mmHg despite anti-hypertensive agents.
21. Prolonged QTc \>450 ms or any ECG changes that interfere with QT interval interpretation
22. Major surgery within 1 month of registration
23. History of myelodysplastic syndrome or leukemia
24. A known hypersensitivity to niraparib, abiraterone acetate, leuprolide, and/or prednisone
25. Active infection or other medical condition that would be a contraindication to prednisone use
26. Patients with known active hepatitis or chronic liver disease including cirrhosis
27. Any condition that in the opinion of the investigator would preclude participation in this study
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Spratt, M.D.

Role: STUDY_CHAIR

Case Western Reserve University - Seidman Comprehensive Cancer Center

William Jackson, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Rogel Cancer Center

Locations

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University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Cornell University

New York, New York, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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HUM00167325

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2019.117

Identifier Type: -

Identifier Source: org_study_id

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