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

Phase 1
Active, not recruiting
Conditions
Prostate Cancer
Interventions
Radiation: Stereotactic body radiotherapy (SBRT)
Registration Number
NCT04194554
Lead Sponsor
University of Michigan Rogel Cancer Center
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
100
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Niraparid Dose EscalationStereotactic body radiotherapy (SBRT)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.
Niraparid Dose EscalationNiraparibDose 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.
Niraparid Dose EscalationLeuprolideDose 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.
Niraparid Dose EscalationAbiraterone AcetateDose 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.
Primary Outcome Measures
NameTimeMethod
Dose-limiting toxicities (Phase 1)Up to 112 days after initial dose of niraparib

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.

Proportion of patients experiencing biochemical failureUp to 3 years after first dose of niraparib

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.

Secondary Outcome Measures
NameTimeMethod
Change in health related quality of lifeFrom baseline up to 3 years after last dose of niraparib

Assessed via EPIC-26 questionnaire

Proportion of patients with undetectable post-treatment PSAMeasured during the end of the 6th cycle of therapy (during week 24 +/- 7 days)

Undetectable PSA will be defined as a PSA ≤0.1 ng/mL.

Prostate cancer specific survivalUp to 5 years after first dose of niraparib

Prostate cancer specific survival will be defined as the duration of time from the start of treatment to death attributable to prostate cancer. Patients who have not died or die of non-prostate cancer related causes will be censored at the last known follow-up or date of death, respectively. Summarized using cumulative incidence or Kaplan-Meier curves as appropriate.

Overall survivalUp to 5 years after first dose of niraparib

Overall survival (OS) will be defined as the duration of time from the start of treatment to death from any cause. Patients who have not died will be censored at the last known follow-up.Summarized using cumulative incidence or Kaplan-Meier curves as appropriate.

Proportion of patients with distant metastasesUp to 5 years after first dose of niraparib

Distant metastases will be defined as any clinical or radiographic evidence of lymph node, bone, or visceral involvement of prostate cancer.

Trial Locations

Locations (6)

University of Michigan Rogel Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Cornell University

🇺🇸

New York, New York, United States

Weill Cornell Medicine

🇺🇸

New York, New York, United States

University Hospitals Seidman Cancer Center

🇺🇸

Cleveland, Ohio, United States

University of Texas Southwestern

🇺🇸

Dallas, Texas, United States

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