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.
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
