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 (NADIR)

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)

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.

Study Overview

• Status: Completed
• Conditions: Prostate Adenocarcinoma; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8
• Intervention / Treatment: Biological: Gonadotrophin Releasing Hormone; Radiation: Intensity-Modulated Radiation Therapy; Drug: Niraparib

Detailed Description

PRIMARY OBJECTIVES:

I. To establish the preferred dose of niraparib in combination with radiation and antiandrogen therapy (ADT). (Phase I) II. To compare the disease-free state, defined as prostate specific antigen (PSA) remaining < 0.1 ng/ml at the end of ADT therapy in men with high risk prostate cancer treated with standard therapy with or without the addition of niraparib. (Phase IIR)

SECONDARY OBJECTIVES:

I. To further establish the safety and toxicity profile of standard treatment with radiation and androgen deprivation therapy specifically, two years from initiation of ADT, plus niraparib at the phase II dose.

II. To compare the overall survival, prostate cancer-specific survival, local/regional or distant progression, and distant metastatic disease rates of standard therapy with or without the addition of niraparib.

EXPLORATORY OBJECTIVE:

I. To identify genomic biomarkers of response to combination therapy with radiation, ADT and PARP inhibition.

OUTLINE: This is a phase I, dose-escalation study of niraparib, followed by a randomized phase II study.

PHASE I: Patients receive niraparib orally (PO) once daily (QD) and receive standard of care gonadotrophin releasing hormone (GnRH) agonist androgen suppression therapy. Treatment with niraparib continues for 12 months, and GnRH agonist therapy for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib and GnRH agonist, patients undergo standard of care intensity-modulated radiation therapy (IMRT) 5 days per week for about 6-9 weeks, depending on type of radiation therapy given, in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) on study.

PHASE II: Patients are randomized to 1 of 2 arms:

ARM I: Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months in the absence of disease progression or unacceptable toxicity. 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 given in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study.

ARM II: Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD for 12 months in the absence of disease progression or unacceptable toxicity. 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 given in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study.

After completion of study treatment, patients are followed up every 6 months for 3 years, then annually for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J E Child Comprehensive Cancer Centre
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85704
      • University of Arizona Cancer Center-Orange Grove Campus
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center-North Campus
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Upland, California, United States, 91786
      • City of Hope Upland
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington University Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Newnan, Georgia, United States, 30265
      • CTCA at Southeastern Regional Medical Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Alton Memorial Hospital
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush MD Anderson Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center-Overland Park
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Columbia, Maryland, United States, 21044
      • Central Maryland Radiation Oncology in Howard County
    • Glen Burnie, Maryland, United States, 21061
      • UM Baltimore Washington Medical Center/Tate Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Bay City, Michigan, United States, 48706
      • McLaren Cancer Institute-Bay City
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Clarkston, Michigan, United States, 48346
      • McLaren Cancer Institute-Clarkston
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Dearborn, Michigan, United States, 48126
      • Henry Ford Medical Center-Fairlane
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Weisberg Cancer Treatment Center
    • Flint, Michigan, United States, 48532
      • McLaren Cancer Institute-Flint
    • Flint, Michigan, United States, 48532
      • Singh and Arora Hematology Oncology PC
    • Lansing, Michigan, United States, 48912
      • Mid-Michigan Physicians-Lansing
    • Lansing, Michigan, United States, 48910
      • Karmanos Cancer Institute at McLaren Greater Lansing
    • Lapeer, Michigan, United States, 48446
      • McLaren Cancer Institute-Lapeer Region
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Cancer Institute-Macomb
    • Novi, Michigan, United States, 48377
      • Henry Ford Medical Center-Columbus
    • Petoskey, Michigan, United States, 49770
      • McLaren Cancer Institute-Northern Michigan
    • Port Huron, Michigan, United States, 48060
      • McLaren-Port Huron
    • Shelby, Michigan, United States, 48315
      • Henry Ford Macomb Health Center - Shelby Township
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • City of Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Kansas City, Missouri, United States, 64154
      • University of Kansas Cancer Center - North
    • Lee's Summit, Missouri, United States, 64064
      • University of Kansas Cancer Center - Lee's Summit
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
  • Montana
    • Great Falls, Montana, United States, 59405
      • Benefis Sletten Cancer Institute
  • New Jersey
    • Cape May Court House, New Jersey, United States, 08210
      • AtlantiCare Health Park-Cape May Court House
    • Egg Harbor, New Jersey, United States, 08234
      • AtlantiCare Surgery Center
    • Newark, New Jersey, United States, 07101
      • Rutgers New Jersey Medical School
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Flushing, New York, United States, 11355
      • The New York Hospital Medical Center of Queens
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Barberton, Ohio, United States, 44203
      • Summa Health System - Barberton Campus
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Medina, Ohio, United States, 44256
      • Summa Health Medina Medical Center
    • West Chester, Ohio, United States, 45069
      • University of Cincinnati Cancer Center-West Chester
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Chadds Ford, Pennsylvania, United States, 19317
      • Christiana Care Health System-Concord Health Center
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Lewisburg, Pennsylvania, United States, 17837
      • Geisinger Medical Oncology-Lewisburg
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • Philadelphia, Pennsylvania, United States, 19124
      • Eastern Regional Medical Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC-Shadyside Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
  • Wisconsin
    • Menomonee Falls, Wisconsin, United States, 53051
      • Froedtert Menomonee Falls Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki Veterans Administration Medical Center
    • Oak Creek, Wisconsin, United States, 53154
      • Drexel Town Square Health Center
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Waukesha, Wisconsin, United States, 53188
      • UW Cancer Center at ProHealth Care
    • West Bend, Wisconsin, United States, 53095
      • Froedtert West Bend Hospital/Kraemer Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Phase I patients: Prior androgen suppression for prostate cancer is not allowed prior to registration
• Phase II patients: Prior androgen suppression for prostate cancer is allowed =< 45 days prior to registration
• Hemoglobin >= 9.0 g/dL (within 90 days prior to registration)
• Platelets >= 100,000 cells/mm^3 (within 90 days prior to registration)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 90 days prior to registration)
• Serum creatinine =<1.5 x upper limit of normal (ULN) OR a calculated creatinine clearance >= 30 mL/min estimated using Cockcroft-Gault equation (within 90 days prior to registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN (within 90 days prior to registration)
• Serum albumin >= 3 g/dL (within 90 days prior to registration)
• Serum potassium >= 3.5 mmol/L (within 90 days prior to registration)
• Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< 1 x ULN (Note: in subjects with Gilberts syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is =< 1.5 x ULN, subject may be eligible) (within 90 days prior to registration)
• Men of child-producing potential must be willing to consent to use effective contraception while on treatment and for at least 3 months afterwards
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

• 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)

• Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter

  • Note that patients who are HIV positive are eligible, provided they have a CD4 count >= 200 cells/microliter within 90 days prior to registration. Patients receiving treatment with highly active antiretroviral therapy (HAART) will not be eligible due to concern for radiosensitization
  • Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be affected by these drugs
• Any history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
• Prior or current treatment with PARP inhibitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I, Dose Level 1 (niraparib, GnRH, IMRT); Patients 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.	Biological: Gonadotrophin Releasing Hormone; Receive standard of care GnRH agonist androgen suppression therapy; Other Names: GnRH; gonadotropin-releasing hormone; LHRH; Luliberin; Gonadorelin; AY-24031; D-His-6-Pro-8-NEt-LHRH; Follicle Stimulating Hormone-Releasing Factor; GN-RH; Gonadoliberin; Gonadorelinum; Hoe- 471; LH-RF; LH-RH; LH/FSH-RF; LH/FSH-RH; Luteinising Hormone-Releasing Factor; Luteinizing Hormone-Releasing Factor; Luteinizing Hormone-Releasing Hormone; Radiation: Intensity-Modulated Radiation Therapy; Undergo standard of care IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Intensity modulated radiation therapy (procedure); Drug: Niraparib; tablet; Other Names: MK-4827; MK4827; MK 4827
Experimental: Phase I, Dose Level 2 (niraparib, GnRH, IMRT); Patients 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.	Biological: Gonadotrophin Releasing Hormone; Receive standard of care GnRH agonist androgen suppression therapy; Other Names: GnRH; gonadotropin-releasing hormone; LHRH; Luliberin; Gonadorelin; AY-24031; D-His-6-Pro-8-NEt-LHRH; Follicle Stimulating Hormone-Releasing Factor; GN-RH; Gonadoliberin; Gonadorelinum; Hoe- 471; LH-RF; LH-RH; LH/FSH-RF; LH/FSH-RH; Luteinising Hormone-Releasing Factor; Luteinizing Hormone-Releasing Factor; Luteinizing Hormone-Releasing Hormone; Radiation: Intensity-Modulated Radiation Therapy; Undergo standard of care IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Intensity modulated radiation therapy (procedure); Drug: Niraparib; tablet; Other Names: MK-4827; MK4827; MK 4827
Experimental: Phase I, Dose Level 3 (niraparib, GnRH, IMRT); Patients 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.	Biological: Gonadotrophin Releasing Hormone; Receive standard of care GnRH agonist androgen suppression therapy; Other Names: GnRH; gonadotropin-releasing hormone; LHRH; Luliberin; Gonadorelin; AY-24031; D-His-6-Pro-8-NEt-LHRH; Follicle Stimulating Hormone-Releasing Factor; GN-RH; Gonadoliberin; Gonadorelinum; Hoe- 471; LH-RF; LH-RH; LH/FSH-RF; LH/FSH-RH; Luteinising Hormone-Releasing Factor; Luteinizing Hormone-Releasing Factor; Luteinizing Hormone-Releasing Hormone; Radiation: Intensity-Modulated Radiation Therapy; Undergo standard of care IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Intensity modulated radiation therapy (procedure); Drug: Niraparib; tablet; Other Names: MK-4827; MK4827; MK 4827
Active Comparator: Phase II, Arm I (GnRH, IMRT); Patients 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.	Biological: Gonadotrophin Releasing Hormone; Receive standard of care GnRH agonist androgen suppression therapy; Other Names: GnRH; gonadotropin-releasing hormone; LHRH; Luliberin; Gonadorelin; AY-24031; D-His-6-Pro-8-NEt-LHRH; Follicle Stimulating Hormone-Releasing Factor; GN-RH; Gonadoliberin; Gonadorelinum; Hoe- 471; LH-RF; LH-RH; LH/FSH-RF; LH/FSH-RH; Luteinising Hormone-Releasing Factor; Luteinizing Hormone-Releasing Factor; Luteinizing Hormone-Releasing Hormone; Radiation: Intensity-Modulated Radiation Therapy; Undergo standard of care IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Intensity modulated radiation therapy (procedure)
Experimental: Phase II, Arm II (niraparib, GnRH, IMRT); Patients 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.	Biological: Gonadotrophin Releasing Hormone; Receive standard of care GnRH agonist androgen suppression therapy; Other Names: GnRH; gonadotropin-releasing hormone; LHRH; Luliberin; Gonadorelin; AY-24031; D-His-6-Pro-8-NEt-LHRH; Follicle Stimulating Hormone-Releasing Factor; GN-RH; Gonadoliberin; Gonadorelinum; Hoe- 471; LH-RF; LH-RH; LH/FSH-RF; LH/FSH-RH; Luteinising Hormone-Releasing Factor; Luteinizing Hormone-Releasing Factor; Luteinizing Hormone-Releasing Hormone; Radiation: Intensity-Modulated Radiation Therapy; Undergo standard of care IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Intensity modulated radiation therapy (procedure); Drug: Niraparib; tablet; Other Names: MK-4827; MK4827; MK 4827

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Alive (Overall Survival)	Survival rates were to be estimated using the Kaplan-Meier method and the treatment arms were to be compared using a log-rank test.	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)	Prostate cancer death rates were to be estimated using the cumulative incidence method, treating deaths due to other causes as competing risks. The treatment arms were to be compared using the Fine-Gray test	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	Complete response was to be determined by a12-core biopsy. Treatment arms were to be compared using a chi-square test.	At two years
Percentage of Participants With Local/Regional or Distant Progression	Progression rates were to be estimated using the cumulative incidence method, treating deaths as competing risks. The treatment arms were to be compared using the Fine-Gray test	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	Distant metastases rates were to be estimated using the cumulative incidence method, treating death as a competing risk. The treatment arms were to be compared using the Fine-Gray test	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.
Percentage of Participants Alive Without Biochemical Progression (Biochemical Progression-free Survival)	Biochemical progression is defined as PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or death from prostate cancer. Biochemical progression-free survival rates were to be estimated using the Kaplan-Meier method and the treatment arms were to be compared using a log-rank test.	From baseline to biochemical progression 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.
Number of Participants by Highest Grade Adverse Event Reported	Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Adverse events were to be categorized as early (within 90 days of completion of radiotherapy) or late (more than 90 days after the completion of radiotherapy).The number of participants per grade was to be compared between the arms for early, late, and all adverse events using chi-square or Fisher exact tests	From baseline to 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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Niraparib/ Preferred Niraparib Dose for Phase II Component	MTD was determined using the classic 3+3 design to determine the safety of each dose level (DL) from the number of participants with dose limiting toxicities (DLTs), starting with DL1. The highest DL deemed safe was to be considered the MTD. The timing of the 3-patient cohorts took into account the previously established safety of concurrent ADT and 200 mg niraparib and the need to more clearly establish the safety of niraparib concurrent with RT. A DLT is defined as any treatment-related gastrointestinal or genitourinary grade 3 or higher AE lasting > 1 week, despite maximal medical interventions, and any treatment-related grade 4 AEs lasting > 1 week. Relationship to treatment was determined by the responsible clinician. Study chairs reviewed possible DLTs for final determination. Niraparib dose level (mg PO QD) definitions [First 8 weeks with ADT, 6-8 weeks with ADT and RT, remaining time of the 12 months]: DL1: 100, 100, 100; DL2: 200, 100, 200; DL3: 200, 200, 200	From start of combined ADT and niraparib to six months
Number of Participants Who Experienced Dose-limiting Toxicities (DLT)	A DLT is defined as any treatment-related gastrointestinal or genitourinary grade 3 or higher AE lasting > 1 week, despite maximal medical interventions, and any treatment-related grade 4 AEs lasting > 1 week. Relationship to treatment was determined by the responsible clinician. Study chairs reviewed possible DLTs for final determination.	From start of combined ADT and niraparib to six months
Percentage of Participants With Gene Alterations Detected by Targeted Exome Sequencing	The percentage of patients with baseline or post-therapy alterations in targeted genes would be reported and the association between the occurrence of alterations and clinical outcomes would be assessed.	From baseline to death or last follow-up, analyzed after all participants have been followed for two years and gene mutation data produced
Percentage of Participants With Gene Expression Determined by High-density Affymetrix Oligonucleotide Array to Profile the Transcriptome of Tumor Samples	The percentage of participants with baseline or post-therapy gene expression and the association between the occurrence of alterations and clinical outcomes would be assessed.	From baseline to death or last follow-up, analyzed after all participants have been followed for two years and gene expression data generated.
Percentage of Participants With Single Nucleotide Polymorphisms From Whole Blood Samples	The percentage of patients with baseline or post-therapy polymorphism would be reported and the association between the occurrence of alterations and clinical outcomes would be assessed.	From baseline to death or last follow-up, analyzed after all participants have been followed for two years and polymorphism data generated.

Collaborators and Investigators

• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: M. D Michaelson, NRG Oncology

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2019
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): December 23, 2025

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Therapeutics; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Gonadotropin-Releasing Hormone; niraparib; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: NRG-GU007 (Other Identifier: CTEP); U10CA180868 (U.S. NIH Grant/Contract); NCI-2019-02260 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No