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NRG-GU007: Randomized phase II trial of niraparib with standard combination radiotherapy and androgen deprivation therapy (ADT) in high-risk prostate cancer (with initial phase I)

Description

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.

Status

Accepting new patients

Primary Study Objective(s)

The primary objectives of this study are to:

  • To establish the preferred dose of niraparib in combination with radiation and antiandrogen therapy (ADT) (Phase I)
  • 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)

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who meet the following 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 >= 60 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 three months afterwards
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Excluding patients who meet the following 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
  • = 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 six months
    • Transmural myocardial infarction within the last six 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
  • 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
     

Accepting new patients

 

Learn more at

clinicaltrials.gov

 

Principal Investigator(s)

David L. Topolsky

Anderson Bauer

Mahdi Taha