Summary

Eligibility
for males ages 18 years and up (full criteria)
Location
at Sacramento, California and other locations
Dates
study started
estimated completion

Description

Summary

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.

Official Title

Randomized Phase II Trial of Niraparib With Standard Combination Radiotherapy and Androgen Deprivation Therapy (ADT) in High Risk Prostate Cancer (With Initial Phase I)

Details

PRIMARY OBJECTIVES:

  1. 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)

SECONDARY OBJECTIVES:

  1. 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 OBJECTIVES:

  1. 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.

Keywords

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 Prostatic Neoplasms Niraparib Hormones Prolactin Release-Inhibiting Factors Follicle Stimulating Hormone Gonadotrophin Releasing Hormone Intensity-Modulated Radiation Therapy

Eligibility

You can join if…

Open to males ages 18 years and up

  • 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/mm3 (within 90 days prior to registration)

  • Absolute neutrophil count (ANC) >= 1.5 x 109/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 3 months afterwards
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

You CAN'T join if...

  • 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
  • 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

Locations

  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento California 95817 United States
  • Cedars Sinai Medical Center accepting new patients
    Los Angeles California 90048 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
NRG Oncology
Links
Sign up for this study
ID
NCT04037254
Phase
Phase 2
Study Type
Interventional
Last Updated