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

NCT ID: NCT04037254

Last Updated: 2025-07-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-08

Study Completion Date

2025-09-26

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Prostate Adenocarcinoma Stage IIC Prostate Cancer AJCC v8 Stage III Prostate Cancer AJCC v8 Stage IIIA Prostate Cancer AJCC v8 Stage IIIB Prostate Cancer AJCC v8 Stage IIIC Prostate Cancer AJCC v8 Stage IVA Prostate Cancer AJCC v8

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Gonadotrophin Releasing Hormone

Intervention Type BIOLOGICAL

Receive standard of care GnRH agonist androgen suppression therapy

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo standard of care IMRT

Niraparib

Intervention Type DRUG

tablet

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.

Group Type EXPERIMENTAL

Gonadotrophin Releasing Hormone

Intervention Type BIOLOGICAL

Receive standard of care GnRH agonist androgen suppression therapy

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo standard of care IMRT

Niraparib

Intervention Type DRUG

tablet

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.

Group Type EXPERIMENTAL

Gonadotrophin Releasing Hormone

Intervention Type BIOLOGICAL

Receive standard of care GnRH agonist androgen suppression therapy

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo standard of care IMRT

Niraparib

Intervention Type DRUG

tablet

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.

Group Type ACTIVE_COMPARATOR

Gonadotrophin Releasing Hormone

Intervention Type BIOLOGICAL

Receive standard of care GnRH agonist androgen suppression therapy

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo standard of care IMRT

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.

Group Type EXPERIMENTAL

Gonadotrophin Releasing Hormone

Intervention Type BIOLOGICAL

Receive standard of care GnRH agonist androgen suppression therapy

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo standard of care IMRT

Niraparib

Intervention Type DRUG

tablet

Interventions

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Gonadotrophin Releasing Hormone

Receive standard of care GnRH agonist androgen suppression therapy

Intervention Type BIOLOGICAL

Intensity-Modulated Radiation Therapy

Undergo standard of care IMRT

Intervention Type RADIATION

Niraparib

tablet

Intervention Type DRUG

Other Intervention Names

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AY-24031 D-His-6-Pro-8-NEt-LHRH Follicle Stimulating Hormone-Releasing Factor GN-RH GnRH Gonadoliberin Gonadorelin Gonadorelinum gonadotropin-releasing hormone Hoe- 471 LH-RF LH-RH LH/FSH-RF LH/FSH-RH LHRH Luliberin Luteinising Hormone-Releasing Factor Luteinizing Hormone-Releasing Factor Luteinizing Hormone-Releasing Hormone IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy MK 4827 MK-4827 MK4827

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

NRG Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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M. D Michaelson

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

University of Arizona Cancer Center-Orange Grove Campus

Tucson, Arizona, United States

Site Status

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Fremont - Rideout Cancer Center

Marysville, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

City of Hope Upland

Upland, California, United States

Site Status

Helen F Graham Cancer Center

Newark, Delaware, United States

Site Status

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Site Status

George Washington University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Grady Health System

Atlanta, Georgia, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Site Status

CTCA at Southeastern Regional Medical Center

Newnan, Georgia, United States

Site Status

Alton Memorial Hospital

Alton, Illinois, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States

Site Status

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Central Maryland Radiation Oncology in Howard County

Columbia, Maryland, United States

Site Status

UM Baltimore Washington Medical Center/Tate Cancer Center

Glen Burnie, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

McLaren Cancer Institute-Bay City

Bay City, Michigan, United States

Site Status

Henry Ford Cancer Institute-Downriver

Brownstown, Michigan, United States

Site Status

McLaren Cancer Institute-Clarkston

Clarkston, Michigan, United States

Site Status

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan, United States

Site Status

Henry Ford Medical Center-Fairlane

Dearborn, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, United States

Site Status

McLaren Cancer Institute-Flint

Flint, Michigan, United States

Site Status

Singh and Arora Hematology Oncology PC

Flint, Michigan, United States

Site Status

Karmanos Cancer Institute at McLaren Greater Lansing

Lansing, Michigan, United States

Site Status

Mid-Michigan Physicians-Lansing

Lansing, Michigan, United States

Site Status

McLaren Cancer Institute-Lapeer Region

Lapeer, Michigan, United States

Site Status

McLaren Cancer Institute-Macomb

Mount Clemens, Michigan, United States

Site Status

Henry Ford Medical Center-Columbus

Novi, Michigan, United States

Site Status

McLaren Cancer Institute-Northern Michigan

Petoskey, Michigan, United States

Site Status

McLaren-Port Huron

Port Huron, Michigan, United States

Site Status

Henry Ford Macomb Health Center - Shelby Township

Shelby, Michigan, United States

Site Status

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Site Status

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Site Status

University of Kansas Cancer Center - North

Kansas City, Missouri, United States

Site Status

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Siteman Cancer Center-South County

St Louis, Missouri, United States

Site Status

Benefis Sletten Cancer Institute

Great Falls, Montana, United States

Site Status

AtlantiCare Health Park-Cape May Court House

Cape May Court House, New Jersey, United States

Site Status

AtlantiCare Surgery Center

Egg Harbor, New Jersey, United States

Site Status

Rutgers New Jersey Medical School

Newark, New Jersey, United States

Site Status

Holy Name Hospital

Teaneck, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

The New York Hospital Medical Center of Queens

Flushing, New York, United States

Site Status

Highland Hospital

Rochester, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

Summa Health System - Akron Campus

Akron, Ohio, United States

Site Status

Summa Health System - Barberton Campus

Barberton, Ohio, United States

Site Status

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Summa Health Medina Medical Center

Medina, Ohio, United States

Site Status

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Christiana Care Health System-Concord Health Center

Chadds Ford, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Geisinger Medical Oncology-Lewisburg

Lewisburg, Pennsylvania, United States

Site Status

Lewistown Hospital

Lewistown, Pennsylvania, United States

Site Status

Eastern Regional Medical Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

UPMC-Shadyside Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, United States

Site Status

Saint Francis Cancer Center

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, United States

Site Status

Self Regional Healthcare

Greenwood, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Greer

Greer, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, United States

Site Status

West Virginia University Healthcare

Morgantown, West Virginia, United States

Site Status

Froedtert Menomonee Falls Hospital

Menomonee Falls, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Zablocki Veterans Administration Medical Center

Milwaukee, Wisconsin, United States

Site Status

Drexel Town Square Health Center

Oak Creek, Wisconsin, United States

Site Status

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, United States

Site Status

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, United States

Site Status

Froedtert West Bend Hospital/Kraemer Cancer Center

West Bend, Wisconsin, United States

Site Status

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2019-02260

Identifier Type: REGISTRY

Identifier Source: secondary_id

NRG-GU007

Identifier Type: OTHER

Identifier Source: secondary_id

NRG-GU007

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NRG-GU007

Identifier Type: -

Identifier Source: org_study_id

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