Testing the Addition of a New Anti-Cancer Drug, Niraparib, to the Usual Treatment (Hormone and Radiation Therapy) for Prostate Cancer With a High Chance of Recurring
Randomized Phase II Trial of Niraparib With Standard Combination Radiotherapy and Androgen Deprivation Therapy (ADT) in High Risk Prostate Cancer (With Initial Phase I) (NADIR*) *Randomized Phase II Trial of Niraparib With Standard Combination Androgen DeprIvation Therapy (ADT) and Radiotherapy in High Risk Prostate Cancer (With Initial Phase I)
3 other identifiers
interventional
22
2 countries
95
Brief Summary
This is a phase I-II trial to find the safety and activity of adding a new drug (neraparib) to the usual treatment (radiation combined with male hormone deprivation therapy) in lowering the chance of prostate cancer growing or returning. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Adding niraparib to the usual care may lower the chance of prostate cancer growing or returning.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2019
Longer than P75 for phase_1
95 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 26, 2019
CompletedFirst Posted
Study publicly available on registry
July 30, 2019
CompletedStudy Start
First participant enrolled
October 8, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2024
CompletedResults Posted
Study results publicly available
July 11, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 23, 2025
CompletedMarch 16, 2026
March 1, 2026
4.7 years
July 26, 2019
June 24, 2025
March 2, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants Disease-free Until Completion of Treatment (2 Years From Start of ADT)
Participants will be considered disease-free if their PSA values remain below 0.1 ng/ml until the completion of treatment. The proportion of patients disease-free at 24 months were to be compared in the two treatment arms using a non-continuity-corrected chi-square test. PSA levels will be assessed prior to the start of RT, at the end of RT, and every three months for 24 months. all PSA values obtained up to and including the two-year landmark must be \< 0.1 ng/ml. Patients who die prior to two years from prostate cancer will be counted as failures. Patients who die from causes other than prostate cancer will be considered non-evaluable for the primary endpoint. Patients still under follow-up but who have a missing PSA value at two years or more than two missing values prior to two years will also be counted as failures.
Baseline to completion of treatment (two years from start of ADT)
Secondary Outcomes (7)
Percent of Participants Alive (Overall Survival)
From baseline to death or last follow-up, analyzed after phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Percentage of Participants With Prostate Cancer Deaths (Prostate Cancer-specific Survival)
From baseline to death or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Percentage of Participants With Pathologic Complete Response (pCR) at Two Years
At two years
Percentage of Participants With Local/Regional or Distant Progression
From baseline to local/regional or distant progression, death, or last follow-up, whichever occurs first, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Percentage of Participants With Distant Metastases
From baseline to distant metastasis, death, or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
- +2 more secondary outcomes
Other Outcomes (5)
Maximum Tolerated Dose (MTD) of Niraparib/ Preferred Niraparib Dose for Phase II Component
From start of combined ADT and niraparib to six months
Number of Participants Who Experienced Dose-limiting Toxicities (DLT)
From start of combined ADT and niraparib to six months
Percentage of Participants With Gene Alterations Detected by Targeted Exome Sequencing
From baseline to death or last follow-up, analyzed after all participants have been followed for two years and gene mutation data produced
- +2 more other outcomes
Study Arms (5)
Phase I, Dose Level 1 (niraparib, GnRH, IMRT)
EXPERIMENTALPatients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity. \*Niraparib dose level 1: 100 mg.
Phase I, Dose Level 2 (niraparib, GnRH, IMRT)
EXPERIMENTALPatients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity. \*Niraparib dose level 2: 100 mg during IMRT 200 mg otherwise.
Phase I, Dose Level 3 (niraparib, GnRH, IMRT)
EXPERIMENTALPatients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment given in the absence of disease progression or unacceptable toxicity. \*Niraparib dose level 3: 200 mg.
Phase II, Arm I (GnRH, IMRT)
ACTIVE COMPARATORPatients undergo standard of care GnRH agonist androgen suppression therapy for 24 months. Beginning 8-28 weeks after starting GnRH agonist, patients undergo IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity.
Phase II, Arm II (niraparib, GnRH, IMRT)
EXPERIMENTALPatients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD (phase I determined dose level) for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity.
Interventions
Receive standard of care GnRH agonist androgen suppression therapy
Undergo standard of care IMRT
tablet
Eligibility Criteria
You may qualify if:
- Histologically confirmed (within 180 days prior to registration) adenocarcinoma of the prostate at high risk for recurrence as determined by the following criteria, according to American Joint Committee on Cancer (AJCC) 8th edition:
- Phase I enrollment
- Gleason \>= 9, PSA =\< 150 ng/mL, any T-stage
- Phase II enrollment
- Gleason \>= 9, PSA =\< 150 ng/mL, any T-stage
- Gleason 8, PSA \< 20 ng/mL, and \>= T2
- Gleason 8, PSA \>= 20-150 ng/mL, any T-stage
- Gleason 7, PSA \>= 20-150 ng/mL, any T-stage
- No distant metastases as evaluated by:
- Bone scan 90 days prior to registration
- Lymph node assessment by computed tomography (CT) or magnetic resonance (MR) of pelvis or nodal sampling within 90 days prior to registration (Please note: Lymph nodes will be considered negative \[N0\] if they are \< 1.5 cm short axis)
- History/physical examination within 90 days prior to registration
- Age \>= 18
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 180 days prior to registration
- Pretreatment serum PSA, obtained prior to any androgen suppression therapy and within 180 days of registration
- +12 more criteria
You may not qualify if:
- PSA \> 150 ng/mL
- Definitive clinical or radiologic evidence of metastatic disease
- Pathologically positive lymph nodes or nodes \> 1.5 cm short axis on CT or MR imaging
- Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason
- Any active malignancy within 2 years of study registration that may alter the course of prostate cancer treatment
- Prior systemic therapy for prostate cancer; note that prior therapy for a different cancer is allowable
- Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields
- Current treatment with first generation anti-androgens (bicalutamide, nilutamide, flutamide). For patients enrolled to phase II, if prior anti-androgens were administered, a washout period of \>= 30 days is required prior to enrollment
- Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Uncontrolled acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition
- Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>=160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
- Prior allergic reaction to the drugs involved in this protocol (including known allergies, hypersensitivity or intolerance to the excipients of niraparib)
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologylead
- National Cancer Institute (NCI)collaborator
Study Sites (95)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
University of Arizona Cancer Center-Orange Grove Campus
Tucson, Arizona, 85704, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Fremont - Rideout Cancer Center
Marysville, California, 95901, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
City of Hope Upland
Upland, California, 91786, United States
Helen F Graham Cancer Center
Newark, Delaware, 19713, United States
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713, United States
George Washington University Medical Center
Washington D.C., District of Columbia, 20037, United States
Grady Health System
Atlanta, Georgia, 30303, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
CTCA at Southeastern Regional Medical Center
Newnan, Georgia, 30265, United States
Alton Memorial Hospital
Alton, Illinois, 62002, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Central Maryland Radiation Oncology in Howard County
Columbia, Maryland, 21044, United States
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland, 21061, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
McLaren Cancer Institute-Bay City
Bay City, Michigan, 48706, United States
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183, United States
McLaren Cancer Institute-Clarkston
Clarkston, Michigan, 48346, United States
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038, United States
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, United States
McLaren Cancer Institute-Flint
Flint, Michigan, 48532, United States
Singh and Arora Hematology Oncology PC
Flint, Michigan, 48532, United States
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan, 48910, United States
Mid-Michigan Physicians-Lansing
Lansing, Michigan, 48912, United States
McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan, 48446, United States
McLaren Cancer Institute-Macomb
Mount Clemens, Michigan, 48043, United States
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377, United States
McLaren Cancer Institute-Northern Michigan
Petoskey, Michigan, 49770, United States
McLaren-Port Huron
Port Huron, Michigan, 48060, United States
Henry Ford Macomb Health Center - Shelby Township
Shelby, Michigan, 48315, United States
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
AtlantiCare Health Park-Cape May Court House
Cape May Court House, New Jersey, 08210, United States
AtlantiCare Surgery Center
Egg Harbor, New Jersey, 08234, United States
Rutgers New Jersey Medical School
Newark, New Jersey, 07101, United States
Holy Name Hospital
Teaneck, New Jersey, 07666, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
The New York Hospital Medical Center of Queens
Flushing, New York, 11355, United States
Highland Hospital
Rochester, New York, 14620, United States
University of Rochester
Rochester, New York, 14642, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Summa Health System - Akron Campus
Akron, Ohio, 44304, United States
Summa Health System - Barberton Campus
Barberton, Ohio, 44203, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Summa Health Medina Medical Center
Medina, Ohio, 44256, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837, United States
Lewistown Hospital
Lewistown, Pennsylvania, 17044, United States
Eastern Regional Medical Center
Philadelphia, Pennsylvania, 19124, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, 15232, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605, United States
Saint Francis Cancer Center
Greenville, South Carolina, 29607, United States
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615, United States
Self Regional Healthcare
Greenwood, South Carolina, 29646, United States
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650, United States
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672, United States
West Virginia University Healthcare
Morgantown, West Virginia, 26506, United States
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Zablocki Veterans Administration Medical Center
Milwaukee, Wisconsin, 53295, United States
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154, United States
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066, United States
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, 53188, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095, United States
Arthur J E Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This study closed accrual permanently without proceeding to the phase II component because the standard of care for prostate cancer in this population substantially evolved and incorporation of the new standard would have required a much larger sample size. Therefore, only phase I results can be reported, appearing as "other pre-specified" outcome measures because although listed as a primary objective in the protocol, they are not explicitly listed as primary or secondary statistical endpoints.
Results Point of Contact
- Title
- Wendy Seiferheld
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
M. D Michaelson
NRG Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 26, 2019
First Posted
July 30, 2019
Study Start
October 8, 2019
Primary Completion
July 1, 2024
Study Completion
December 23, 2025
Last Updated
March 16, 2026
Results First Posted
July 11, 2025
Record last verified: 2026-03