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

NCT04194554 | Active Not Recruiting Phase 1 FDA Drug FDA Device

• 2 other identifiers: UMCC 2019.117HUM00167325
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities (Phase 1)

  The proportion of patients at each dose level with dose-limiting toxicity (DLT), defined as any treatment related grade 3-5 adverse event experienced within the first 4 treatment cycles (112 days), assessed per NCI's CTCAE version 5.0.

  Up to 112 days after initial dose of niraparib

• Proportion of patients experiencing biochemical failure

  Change in PSA level from the beginning of study treatment for up to 3 years later will determine the biochemical failure rate. Biochemical failure will be defined using the Phoenix definition of the PSA nadir + 2 ng/mL.

  Up to 3 years after first dose of niraparib

Secondary Outcomes (5)

• Change in health related quality of life

  From baseline up to 3 years after last dose of niraparib

• Proportion of patients with undetectable post-treatment PSA

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

• Proportion of patients with distant metastases

  Up to 5 years after first dose of niraparib

• Prostate cancer specific survival

  Up to 5 years after first dose of niraparib

• Overall survival

  Up to 5 years after first dose of niraparib

Study Arms (1)

Niraparid Dose Escalation

EXPERIMENTAL

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.

Drug: Niraparib; Drug: Leuprolide; Drug: Abiraterone Acetate; Radiation: Stereotactic body radiotherapy (SBRT)

Interventions

Niraparib DRUG

given PO per dose escalation schedule

Niraparid Dose Escalation

Leuprolide DRUG

22.5 mg q3 month

Niraparid Dose Escalation

Abiraterone Acetate DRUG

1000 mg daily

Niraparid Dose Escalation

Stereotactic body radiotherapy (SBRT) RADIATION

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

Also known as: Ultra-hypofractionated radiotherapy

Niraparid Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologic biopsy proven adenocarcinoma of the prostate
• 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
• Age ≥ 18
• ECOG \< 1
• Adequate organ and marrow function as defined per protocol.
• 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.
• International Prostate Symptoms Score (IPSS) ≤ 20
• Medically fit for treatment and agreeable to follow-up
• Ability to understand and the willingness to sign a written informed consent

You may not qualify if:

• Clinical or radiographic evidence of distant metastatic disease by CT/bone scan
• Clinical or radiographic evidence of high probability of clinical T4 disease
• Prostate gland size \>80 cc measured by ultrasound or MRI
• Prominent median lobe assessed by treating physician
• Lack of tissue from biopsy to be sent for correlative studies
• Any prior treatment for prostate cancer (incudes history of TURP within 5 years of enrollment, chemotherapy, radiation therapy, or anti-androgen therapy)
• Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies.
• 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.
• History of prior pelvic radiation therapy
• Concurrent treatment with strong CYP3A4 inducers such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital
• Enrollment concurrently in another investigational drug study within 1 month of registration
• History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer
• History of or active Crohn's disease or ulcerative colitis
• Contraindication to or inability to tolerate MRIs
• Patients with severe depression

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (6)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55901, United States

Location

Cornell University

New York, New York, 10065, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

niraparib; Leuprolide; Abiraterone Acetate; Radiosurgery

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Daniel Spratt, M.D.

  Case Western Reserve University - Seidman Comprehensive Cancer Center

  STUDY CHAIR

• William Jackson, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Time to Event Continual Reassessment Method (TITE-CRM) dose-finding clinical trial design.

Study Record Dates

• First Submitted: December 9, 2019
• First Posted: December 11, 2019
• Study Start: November 6, 2020
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2029
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The time frame for data sharing will begin 12 months after the initial publication and continue until 36 months after publication in ClinicalTrials.gov.
• Access Criteria: Once the final results of the trial have been reported parties interested in accessing the data should contact the trial PI (Dr. Daniel Spratt) to discuss any potential data sharing requests. An analysis plan is required and intended use of the data must be disclosed. Only de-identified data may be shared and all agreements must comply with current policies of both parties to share data.

Locations

US (6)