Prostate Cancer Clinical Trial
Niraparib With Standard Combination Radiation Therapy and Androgen Deprivation Therapy in Treating Patients With High Risk Prostate Cancer
This phase II trial studies the side effects and best dose of niraparib, and to see how well it works in combination with standard of care radiation therapy and hormonal therapy (androgen deprivation therapy) in treating patients with prostate cancer that has a high chance of coming back (high risk). Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Adding niraparib to the usual treatments of radiation therapy and hormonal therapy may lower the chance of prostate cancer growing or returning.
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 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)
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.
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 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.
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 â‰¥ 9, PSA â‰¤ 150 ng/mL, any T-stage
Phase II enrollment
Gleason â‰¥ 9, PSA â‰¤ 150 ng/mL, any T-stage
Gleason 8, PSA < 20 ng/mL, and â‰¥ T2
Gleason 8, PSA â‰¥ 20-150 ng/mL, any T-stage
Gleason 7, PSA â‰¥ 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 â‰¤ 45 days prior to registration
Hemoglobin â‰¥ 9.0 g/dL (within 90 days prior to registration)
Platelets â‰¥ 100,000 cells/mm^3 (within 90 days prior to registration)
Absolute neutrophil count (ANC) â‰¥ 1.5 x 10^9/L (within 90 days prior to registration)
Serum creatinine â‰¤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) â‰¤ 3.0 x ULN (within 90 days prior to registration)
Serum albumin â‰¥ 3 g/dL (within 90 days prior to registration)
Serum potassium â‰¥ 3.5 mmol/L (within 90 days prior to registration)
Serum total bilirubin â‰¤ 1.5 x ULN or direct bilirubin â‰¤ 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 â‰¤ 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
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. Please see Niraparib IB for details.)
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 Myelodysplasitc Syndromes (MDS)/ Acute Myeloid Leukemia (AML).
Prior or current treatment with PARP inhibitor
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There are 92 Locations for this study
Tucson Arizona, 85704, United States
Tucson Arizona, 85719, United States
Duarte California, 91010, United States
Marysville California, 95901, United States
Sacramento California, 95817, United States
Upland California, 91786, United States
Atlanta Georgia, 30303, United States
Atlanta Georgia, 30322, United States
Atlanta Georgia, 30342, United States
Newnan Georgia, 30265, United States
Baltimore Maryland, 21201, United States
Columbia Maryland, 21044, United States
Glen Burnie Maryland, 21061, United States
Brownstown Michigan, 48183, United States
Clinton Township Michigan, 48038, United States
Dearborn Michigan, 48126, United States
Detroit Michigan, 48202, United States
Novi Michigan, 48377, United States
Shelby Michigan, 48315, United States
West Bloomfield Michigan, 48322, United States
Jackson Mississippi, 39216, United States
Cape May Court House New Jersey, 08210, United States
Egg Harbor Township New Jersey, 08234, United States
Teaneck New Jersey, 07666, United States
Buffalo New York, 14263, United States
Flushing New York, 11355, United States
Stony Brook New York, 11794, United States
Philadelphia Pennsylvania, 19124, United States
Charleston South Carolina, 29425, United States
Greenwood South Carolina, 29646, United States
Morgantown West Virginia, 26506, United States
Milwaukee Wisconsin, 53295, United States
Calgary Alberta, T2N 4, Canada
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