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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

Trial Status: Active

This is a phase I-II trial to find the safety and activity of adding a new drug (neratinib) 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.

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
  • 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 mg/dL (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

Arizona

Tucson
University of Arizona Cancer Center-North Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-327-2873
University of Arizona Cancer Center-Orange Grove Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: 520-694-8900

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-826-4673
Los Angeles
Cedars Sinai Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 310-423-8965
Sacramento
University of California Davis Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 916-734-3089

District of Columbia

Washington
George Washington University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 202-741-2981

Georgia

Atlanta
Emory Saint Joseph's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-851-7115
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-778-1868
Grady Health System
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-489-9164
Newnan
CTCA at Southeastern Regional Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 770-400-6629

Illinois

Chicago
Northwestern University
Status: ACTIVE
Contact: Site Public Contact
Phone: 312-695-1301
Rush University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 312-942-5498
Urbana
Carle Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-237-1225

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671
Overland Park
University of Kansas Cancer Center-Overland Park
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-888-8823
Columbia
Central Maryland Radiation Oncology in Howard County
Status: ACTIVE
Contact: Site Public Contact
Phone: 443-546-1300
Glen Burnie
UM Baltimore Washington Medical Center / Tate Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 410-553-8100

Michigan

Bay City
McLaren Cancer Institute-Bay City
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Brownstown
Henry Ford Cancer Institute-Downriver
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-916-3721
Clarkston
McLaren Cancer Institute-Clarkston
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Clinton Township
Henry Ford Macomb Hospital-Clinton Township
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-916-3721
Dearborn
Henry Ford Medical Center-Fairlane
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-916-3721
Detroit
Henry Ford Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-916-3721
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Farmington Hills
Weisberg Cancer Treatment Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Flint
McLaren Cancer Institute-Flint
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Singh and Arora Hematology Oncology PC
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Lansing
McLaren-Greater Lansing
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Mid-Michigan Physicians-Lansing
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Lapeer
McLaren Cancer Institute-Lapeer Region
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Mount Clemens
McLaren Cancer Institute-Macomb
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Novi
Henry Ford Medical Center-Columbus
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-916-3721
Petoskey
McLaren Cancer Institute-Northern Michigan
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Port Huron
McLaren-Port Huron
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790
Shelby Township
Henry Ford Macomb Health Center - Shelby Township
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-916-1784
West Bloomfield
Henry Ford West Bloomfield Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-916-3721

Mississippi

Jackson
University of Mississippi Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 601-815-6700

Missouri

Creve Coeur
Siteman Cancer Center at West County Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606
Kansas City
University of Kansas Cancer Center - North
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671
Lee's Summit
University of Kansas Cancer Center - Lee's Summit
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671
Saint Louis
Siteman Cancer Center-South County
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606
Washington University School of Medicine
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606
Saint Peters
Siteman Cancer Center at Saint Peters Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606

Montana

Great Falls
Benefis Healthcare- Sletten Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060

New Jersey

Cape May Court House
AtlantiCare Health Park-Cape May Court House
Status: ACTIVE
Contact: Site Public Contact
Phone: 888-369-2427
Egg Harbor Township
AtlantiCare Surgery Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 609-748-7200
Newark
Rutgers New Jersey Medical School
Status: ACTIVE
Contact: Site Public Contact
Phone: 732-235-7356
Teaneck
Holy Name Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 201-833-6312

New York

Buffalo
Roswell Park Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-767-9355
Rochester
Highland Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 585-341-8113
University of Rochester
Status: ACTIVE
Contact: Site Public Contact
Phone: 585-275-5830
Stony Brook
Stony Brook University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-862-2215

Ohio

Akron
Summa Health System - Akron Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: 330-375-4221
Cleveland
Case Western Reserve University
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 405-271-8777

Pennsylvania

Danville
Geisinger Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 570-271-5251
Lewisburg
Geisinger Medical Oncology-Lewisburg
Status: ACTIVE
Contact: Site Public Contact
Phone: 570-374-8555
Lewistown
Lewistown Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 717-242-7703
Philadelphia
Eastern Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 412-339-5294
Pittsburgh
UPMC-Shadyside Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 412-621-2334
Wilkes-Barre
Geisinger Wyoming Valley / Henry Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 570-271-5251

South Carolina

Charleston
Medical University of South Carolina
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 843-792-9321
Greenville
Prisma Health Cancer Institute - Eastside
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-522-2066
Prisma Health Cancer Institute - Faris
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-522-2066
Saint Francis Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-603-6213
Greenwood
Self Regional Healthcare
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 864-725-4771
Greer
Prisma Health Cancer Institute - Greer
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-522-2066
Seneca
Prisma Health Cancer Institute - Seneca
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-522-2066

West Virginia

Morgantown
West Virginia University Healthcare
Status: ACTIVE
Contact: Site Public Contact
Phone: 304-293-7374

Wisconsin

Menomonee Falls
Froedtert Menomonee Falls Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 262-257-5100
Milwaukee
Medical College of Wisconsin
Status: ACTIVE
Contact: Site Public Contact
Phone: 414-805-3666
Zablocki Veterans Administration Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 888-469-6614
Oconomowoc
ProHealth Oconomowoc Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 262-928-7878
Waukesha
UW Cancer Center at ProHealth Care
Status: ACTIVE
Contact: Site Public Contact
Phone: 262-928-5539
West Bend
Froedtert West Bend Hospital / Kraemer Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 414-805-0505

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.

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.

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.

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

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
NRG Oncology

Principal Investigator
M. Dror Michaelson

  • Primary ID NRG-GU007
  • Secondary IDs NCI-2019-02260
  • Clinicaltrials.gov ID NCT04037254