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About
This phase II trial studies the effect of androgen ablation therapy with or without niraparib after standard of care radiation therapy in treating patients with prostate cancer that has not spread to other parts of the body (localized) or that has spread to nearby tissue or lymph nodes (locally advanced). Androgen ablation therapy (also known as hormone therapy) lowers the levels of male hormones called androgens in the body. Androgens stimulate prostate cancer cells to grow. There are 2 types of androgen ablation therapy given in this study: AAP + ADT and Apa + ADT. AAP + ADT is the treatment combination of the drugs abiraterone acetate and prednisone (AAP) given with androgen deprivation therapy (ADT, also known as androgen deprivation therapy or androgen suppression medication, which is used as standard of care to lower testosterone levels in men with high risk localized or metastatic prostate cancer). Apa + ADT is the treatment combination of the drug apalutamide (Apa) given with ADT. Androgen ablation therapy with or without niraparib after radiation therapy may help to control the disease in patients with prostate cancer.
Full description
PRIMARY OBJECTIVE:
I. Determine the efficacy of addition of adjuvant niraparib to maximal androgen signaling ablation (AAP + ADT) versus maximal androgen signaling ablation alone (Apa + ADT) following definitive radiation therapy (XRT) for biomarker-selected men with poor histopathologic response to neoadjuvant androgen signaling ablative therapy.
SECONDARY OBJECTIVES:
I. Determine the safety and tolerability of adjuvant niraparib with androgen ablation versus androgen ablation alone following definitive XRT in the study population.
II. Determine the impact of the addition of adjuvant niraparib to maximal androgen signaling ablation (AAP + ADT) versus maximal androgen signaling ablation alone (Apa + ADT) following definitive XRT for biomarker-selected men with good and poor histopathologic response to neoadjuvant androgen signaling ablative therapy on overall survival III. Determine the impact of the niraparib + AAP + ADT and Apa+ADT treatment on eugonadal (non-castrate levels of testosterone) progression free survival.
IV. Determine the impact of favorable versus unfavorable histologic response on progression-free survival (PFS) in men who received maximal androgen signaling ablation prior to definitive radiation.
CORRELATIVE OBJECTIVE:
I. Collect and archive solid and liquid tumor samples, as well as normal blood samples for germline deoxyribonucleic acid (DNA), immune, and metabolic profiles from all study patients for later hypothesis generating associations. Assess the relationship of histopathologic score with circulating markers and clinical outcomes of progression free survival for biomarker discovery.
OUTLINE:
PART 1 NEOADJUVANT PHASE (CYCLES 1-3): Patients receive apalutamide orally (PO) once daily (QD) on days 1-28, and physician's choice ADT. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
PART 2 RADIATION PHASE (CYCLES 4-6): Within 30 days of completing Part 1, patients undergo radiation therapy. Patients also receive apalutamide PO QD on days 1-28 and physician's choice ADT. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
PART 3 ADJUVANT PHASE (CYCLES 7 AND BEYOND): Patients with favorable response after Part 2 continue Apa + ADT. Patients with unfavorable response after Part 2 are randomized to 1 of 2 groups.
GROUP A: Patients receive apalutamide PO QD on days 1-28 and physician's choice ADT. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
GROUP B: Patients receive abiraterone acetate PO QD, prednisone PO twice daily (BID), physician's choice ADT, and niraparib PO QD. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 14 days, at 30-90 days, and then every 3 months for 3 years.
Enrollment
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Inclusion criteria
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:
Primary purpose
Allocation
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200 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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