Apalutamide in Treating Patients With Prostate Cancer Before Radical Prostatectomy

Study Overview
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Brief Summary
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This phase II trial studies how well apalutamide works in treating patients with prostate cancer before radical prostatectomy. Androgen can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by lowering the amount of androgen the body makes and may make it less likely for patients to receive radiation therapy after surgery.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine whether 6 months (24 weeks) of neoadjuvant apalutamide prior to prostatectomy for intermediate risk prostate cancer results in a reduction of aggregate pathologic risk features that drive post-operative radiotherapy recommendations from 35% to 15%. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of 6 months (24 weeks) neoadjuvant apalutamide followed by radical prostatectomy for intermediate risk prostate cancer. II. To estimate the frequency of clinical complete responses and near complete responses (currently defined as < 6 mm total tumor volume). III. To characterize the molecular features of the treated prostate cancers and link them to morphologic characterization. IV. To measure the 3-5 year biochemical recurrence rate of treated patients as a baseline to inform a larger phase III trial. OUTLINE: Patients receive apalutamide orally (PO) daily for 24 weeks in the absence of disease progression or unacceptable toxicity. Within 2 weeks of completing apalutamide, patients undergo radical prostatectomy. After completion of study treatment, patients are followed up at 12 months.

Official Title
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A Single Arm Study of 6-Months Neoadjuvant Apalutamide Prior to Radical Prostatectomy in Intermediate Risk Patients to Reduce the Frequency of Pathologic Features That Drive Post-Operative Radiation Therapy

Conditions
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Prostate Adenocarcinoma, Stage IIB Prostate Cancer AJCC v8

Intervention / Treatment
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* Drug: Apalutamide
* Other: Quality-of-Life Assessment
* Procedure: Radical Prostatectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent Histologically confirmed adenocarcinoma of the prostate A minimum of 10 core biopsies have been performed at baseline and available. A prostate biopsy within 6 months from screening is allowed for entry requirements. Biopsies performed within 6-12 months from screening are acceptable if the treating physician would allow treatment without further biopsy. Patients must meet intermediate risk criteria from Gleason score, T stage, and prostate-specific antigen (PSA) value by National Comprehensive Cancer Network (NCCN) criteria: cT2b-T2c or Gleason 7 (3+4 or 4+3) or PSA 10-20 ng/mL. In addition, the Gleason 3+4 or 4+3 must be present Pathology review at MD Anderson Cancer Center. The volume of disease must be high enough for the surgeon to agree to include an extended template pelvic lymph node dissection Serum testosterone > 200 ng/mL Patient and urologist must agree that patient is suitable for prostatectomy No evidence of metastases on imaging. This risk group does not require metastatic studies, but if performed they must be negative (as determined by urologist or radiologist). Suspicious lymph nodes permissible if < 10 mm Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Hemoglobin >= 10.0 g/dL Platelet count >= 100,000 x 10^9/microliter Glomerular filtration rate (GFR) >= 45 mL/min Serum potassium >= 3.5 mmol/L Serum albumin >= 3.0 g/dL Able to swallow the study drug whole as a tablet Serum bilirubin < 1.5 x upper limit of normal (ULN); 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 Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN Normal coagulation profile and no history of substantial non-iatrogenic bleeding diathesis Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug Exclusion Criteria: Histological variants in the primary tumor, other than adenocarcinoma; for example: neuroendocrine tumor, small cell or sarcomatoid Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection PSA is > than 20 ng/mL (NOTE: unless other valid PSAs were =< 20 and the treating physician considers a value > 20 related to the biopsy or other non-malignant cause. The treating physician must consider the patient intermediate risk in aggregate) Uncontrolled hypertension. Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy. Note that this is NOT a criterion related to particular blood pressure (BP) results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes Active or symptomatic viral hepatitis or chronic liver disease Clinically significant heart disease as evidenced by myocardial infarction, arterial thrombotic events in the past 6 months, severe or unstable angina, class III-IV New York Heart Association heart failure Other malignancy, except non-melanoma skin cancer, that is active or has a >= 30% probability of recurrence within 12 months History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug Known history of pituitary and/or adrenal disease (or dysfunction) Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or luteinizing hormone-releasing hormone (LHRH) agonists/antagonists Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV) Patients who are not appropriate surgical candidates for radical prostatectomy based on the evaluation of co-existent medical diseases and competing potential causes of death (such as but not limited to, unstable angina, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, uncontrolled hypertension) History of seizure, seizure disorder, or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (day 1 visit). Drugs may not be used which are known to decrease the seizure threshold

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (apalutamide, radical prostatectomy)<br>Patients receive apalutamide PO daily for 24 weeks in the absence of disease progression or unacceptable toxicity. Within 2 weeks of completing apalutamide, patients undergo radical prostatectomy. | Drug: Apalutamide<br>* Given PO<br>* Other names: JNJ-56021927;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Procedure: Radical Prostatectomy<br>* Undergo radical prostatectomy<br>* Other names: Prostatovesiculectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aggregate Pathologic Risk Features | Aggregate pathologic risk features defined as any of the 3 pathologic staging features on a radical prostatectomy specimen that indicate elevated future risk of a patient needing pelvic radiation therapy. It can be any single or combination of the three. The three drivers per AUA/ASTRO guidelines are positive surgical margins, extraprostatic extension, and/or seminal vesicle invasion. These will be determined by a single expert genitourinary pathologist. The primary objective is to show a 20% decrease in these aggregate pathologic features. | 2 weeks after last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE_) of Neoadjuvant Apalutamide Followed by Radical Prostatectomy | AE scored using CTC AE Version 4.0 for toxicity and adverse event reporting. | Beginning of study drug up to 6 months | 
| Estimation of the frequency of clinical complete responses (pT0) and near complete responses (<6mm total tumor volume) | The proportion of patients having clinical complete responses and near complete responses estimated, along with the exact 95% confidence interval. The Kaplan-Meier method used to assess time to biochemical recurrence and to estimate the rate of biochemical recurrence. | 24 weeks up to 1 year after surgery | 
| To characterize the molecular features of the treated prostate cancers and link them to morphologic characterization |  | 5 years | 
| Biochemical Recurrence Rate | The Kaplan-Meier method used to assess time to biochemical recurrence. | 3 to 5 years | 
| Quality of Life | The EPIC quality of life data summarized by domains and compared pre- and post-treatment using paired t-test or Wilcoxon signed rank test as appropriate. | 3 to 5 years |