| Eligibility |
Inclusion Criteria:
- Completion of informed consent prior to any study specific procedures. Consent may be
done remotely.
- Patients must agree to tissue collection for correlative studies at the specified
timepoints
- Male aged 18 years and above
- Histologically or cytologically confirmed prostate carcinoma
- Localized or regional high-risk disease as defined by at least one of the following
features: Prostate specific antigen (PSA) > 20 ng/mL, T3a or higher, grade group 4-5
(i.e. Gleason score = 8) as per National Comprehensive Cancer Network (NCCN) Prostate
Cancer Version 2.2020 for high risk or very high risk prostate cancer, and/or regional
lymph nodes positive for prostate cancer
- Planned for definitive treatment of local regional prostate cancer using XRT and
androgen ablation
- Willing to undergo ongoing medical castration to maintain testosterone levels of = 50
ng/dL (= 2.0 nM) throughout systemic treatment or have undergone bilateral orchiectomy
- Eastern Cooperative Oncology Group (ECOG) performance status of = 2. Patients must
have adequate organ and bone marrow function measured within 7 days prior to treatment
registration as defined below:
- Hemoglobin = 10.0 g/dL
- Absolute neutrophil count (ANC) = 1.5 x 10^9/L
- White blood cells (WBC) > 3 x 10^9/L
- No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
on peripheral blood smear
- Platelet count = 100 x 10^9/L
- Total bilirubin = 1.5 x institutional upper limit of normal (ULN) (except for patients
with known Gilbert's disease). (Note: In subjects with Gilbert's 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.)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) = 2.5 x
institutional upper limit of normal
- Calculated creatinine clearance (Cockcroft-Gault Equation) = 30 mL/min
- Serum Albumin = 3.0
- Serum potassium = 3.5 mmol/L
- Able to swallow study drugs whole as a tablet/capsule
- Patients who have partners of childbearing potential (e.g. female that has not been
surgically sterilized or who are not amenorrheic for = 12 months) must be willing to
use two methods of birth control including adequate barrier protection during the
study and for 4 months after last dose of niraparib, abiraterone acetate, and/or
apalutamide administration. In addition men should not donate sperm during this
period. Please note that the efficacy of hormonal contraception may be decreased if
administered with niraparib, abiraterone acetate, and/or apalutamide
- Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up
- Medications known to lower the seizure threshold must be discontinued or substituted
at least 4 weeks prior to study entry
Exclusion Criteria:
- Any prior systemic treatment for prostate cancer with the exception of ADT started
within 6 months of trial enrollment. Any prior PARP inhibitor therapy
- Patients who have prostate cancer with distant metastatic disease
- Patients who have had prior major surgery (prostatectomy) or radiotherapy for the
treatment of prostate cancer
- Any unresolved toxicity (Common Terminology Criteria for Adverse Events [CTCAE] grade
= 2) from previous anti-cancer therapies
- History or current diagnosis of MDS/AML, and/or history of any malignancy [other than
the one treated in this study] which has a = 30% probability of recurrence within 24
months (except for adequately treated non-melanoma skin cancer, curatively treated
in-situ cancer of the cervix or Ta urothelial carcinomas)
- Active uncontrolled infection (patients completing a course of antibiotic or antiviral
therapy whose infection is deemed to be controlled may be allowed on study after
discussion with the principal investigator [PI]; the PI will serve as the final
arbiter regarding eligibility)
- Active or symptomatic viral hepatitis or chronic liver disease
- Active pneumonitis or extensive bilateral lung disease of non-malignant etiology
- Any underlying medical or psychiatric condition, which in the opinion of the
Investigator, will make the administration of study drug hazardous or obscure the
interpretation of adverse events. Examples include, but are not limited to superior
vena cava syndrome, extensive bilateral lung disease on high resolution computed
tomography (HRCT) scan, uncontrolled seizures, history of allogeneic organ transplant,
history of primary immunodeficiency or any psychiatric disorder that prohibits
obtaining informed consent
- Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of study medication
- Patients with a known hypersensitivity to niraparib, apalutamide, and/or abiraterone
acetate
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (e.g. infectious disease) illness
- Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within
1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or
other benign central nervous system [CNS] or meningeal disease which may require
treatment with surgery or radiation therapy)
- Severe or unstable angina, myocardial infarction (within 6 months prior to
enrollment), symptomatic congestive heart failure, arterial or venous thromboembolic
events (e.g., pulmonary embolism, cerebrovascular accident including transient
ischemic attacks), uncontrolled hypertension, or clinically significant ventricular
arrhythmias within 6 months prior to randomization
- Current evidence of any of the following:
- Gastrointestinal disorder affecting absorption
- Active uncontrolled infection (e.g., human immunodeficiency virus [HIV] or viral
hepatitis)
- Any chronic medical condition requiring a higher dose of corticosteroid than 10
mg prednisone/prednisolone once daily
- Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If
a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate
dosing frequency
- Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a
narrow therapeutic index. If an alternative treatment cannot be used, exercise
caution and consider a dose reduction of the concomitant CYP2D6 substrate
- Baseline moderate and severe hepatic impairment (Child-Pugh class B & C)
- Any condition that in the opinion of the investigator, would preclude
participation in this study
|
