Prostate Adenocarcinoma, Stage IIB Prostate Cancer AJCC v8
Conditions
Brief summary
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
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.
Interventions
DRUGApalutamide
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
PROCEDURERadical Prostatectomy
Undergo radical prostatectomy
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Surgical Pathology Features at Risk of Pelvic Radiation Therapy | Assessed at time of surgical specimen microscopic evalution Assessed at time of surgical specimen microscopic evaluation | To determine whether 6 months (24 weeks) of neoadjuvant apalutamide prior to prostatectomy for intermediate risk prostate cancer results in a reduction of surgical pathology features at risk of pelvic RT, defined as pT3a, pT3b stage, N1 and/or positive surgical margin. All patients who receive at least 9 weeks of neoadjuvant therapy of apalutamide and undergo radical prostatectomy will be evaluable for the primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of 6 Months Neoadjuvant Apalutamide Followed by Radical Prostatectomy | From initiation of apalutamide through 30 days post-surgery. For those participants who did not have surgery, we assessed the reported AEs until 30 days after the last dose of apalutamide. | Incidence of treatment emergent adverse events (TEAEs). All patients who receive any dose of apalutamide will be evaluable for safety. |
| Clinical Complete Responses (pT0) and "Near" Complete Responses (<6mm Total Tumor Volume) | Assessed at time of surgical specimen microscopic evaluation | The numbers of patients with \<6 mm total tumor volume in their surgical specimens, assessed by study Pathologist. |
| Biochemical Recurrence Rate | From surgery through 3-year post-op follow up | Number of patients who had a PSA value of equal of more than 0.2 ng/dL after surgery and through 3 years of follow up. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJohn W Davis
M.D. Anderson Cancer Center
Participant flow
Recruitment details
Between May 2018 and February 2020, 45 men were enrolled, initiated preoperative apalutamide, and were evaluable for safety outcomes. Of those, two patients withdrew consent prior to surgery, one patient stopped apalutamide at \<9 weeks after initiation, and two patients did not undergo a Radical Prostatectomy (RP)
Participants by arm
| Arm | Count |
|---|---|
| Open label apalutamide and surgery apalutamide 240 mg/day orally for a total duration of 24 weeks, and RP plus ePLND was performed within 3 weeks of completing apalutamide | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | Open label apalutamide and surgery |
|---|---|
| Age, Continuous | 60 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 45 |
| other Total, other adverse events | 45 / 45 |
| serious Total, serious adverse events | 2 / 45 |
Outcome results
Primary
Number of Adverse Surgical Pathology Features at Risk of Pelvic Radiation Therapy
To determine whether 6 months (24 weeks) of neoadjuvant apalutamide prior to prostatectomy for intermediate risk prostate cancer results in a reduction of surgical pathology features at risk of pelvic RT, defined as pT3a, pT3b stage, N1 and/or positive surgical margin. All patients who receive at least 9 weeks of neoadjuvant therapy of apalutamide and undergo radical prostatectomy will be evaluable for the primary endpoint.
Time frame: Assessed at time of surgical specimen microscopic evalution Assessed at time of surgical specimen microscopic evaluation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open label apalutamide and surgery | Number of Adverse Surgical Pathology Features at Risk of Pelvic Radiation Therapy | 16 Participants |
Secondary
Biochemical Recurrence Rate
Number of patients who had a PSA value of equal of more than 0.2 ng/dL after surgery and through 3 years of follow up.
Time frame: From surgery through 3-year post-op follow up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open label apalutamide and surgery | Biochemical Recurrence Rate | 6 Participants |
Secondary
Clinical Complete Responses (pT0) and Near Complete Responses (<6mm Total Tumor Volume)
The numbers of patients with \<6 mm total tumor volume in their surgical specimens, assessed by study Pathologist.
Time frame: Assessed at time of surgical specimen microscopic evaluation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open label apalutamide and surgery | Clinical Complete Responses (pT0) and Near Complete Responses (<6mm Total Tumor Volume) | 0 Participants |
Secondary
Safety and Tolerability of 6 Months Neoadjuvant Apalutamide Followed by Radical Prostatectomy
Incidence of treatment emergent adverse events (TEAEs). All patients who receive any dose of apalutamide will be evaluable for safety.
Time frame: From initiation of apalutamide through 30 days post-surgery. For those participants who did not have surgery, we assessed the reported AEs until 30 days after the last dose of apalutamide.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open label apalutamide and surgery | Safety and Tolerability of 6 Months Neoadjuvant Apalutamide Followed by Radical Prostatectomy | Any TEAEs | 45 Participants |
| Open label apalutamide and surgery | Safety and Tolerability of 6 Months Neoadjuvant Apalutamide Followed by Radical Prostatectomy | Grade ≥3 TEAE | 13 Participants |
| Open label apalutamide and surgery | Safety and Tolerability of 6 Months Neoadjuvant Apalutamide Followed by Radical Prostatectomy | TEAE leading to discontinuation | 4 Participants |