Clinical Trials /

Apalutamide in Treating Patients With Prostate Cancer Before Radical Prostatectomy

NCT03412396

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Apalutamide in Treating Patients With Prostate Cancer Before Radical Prostatectomy
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 2015-0693
  • SECONDARY ID: NCI-2018-00902
  • SECONDARY ID: 2015-0693
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03412396

Conditions

  • Prostate Adenocarcinoma
  • Stage IIB Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
ApalutamideARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927Treatment (apalutamide, radical prostatectomy)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (apalutamide, radical prostatectomy)ExperimentalPatients 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.
  • Apalutamide

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Aggregate Pathologic Risk Features
Time Frame:2 weeks after last dose of study drug
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Adverse Events (AE_) of Neoadjuvant Apalutamide Followed by Radical Prostatectomy
Time Frame:Beginning of study drug up to 6 months
Safety Issue:
Description:AE scored using CTC AE Version 4.0 for toxicity and adverse event reporting.
Measure:Estimation of the frequency of clinical complete responses (pT0) and "near" complete responses (<6mm total tumor volume)
Time Frame:24 weeks up to 1 year after surgery
Safety Issue:
Description: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.
Measure:To characterize the molecular features of the treated prostate cancers and link them to morphologic characterization
Time Frame:5 years
Safety Issue:
Description:
Measure:Biochemical Recurrence Rate
Time Frame:3 to 5 years
Safety Issue:
Description:The Kaplan-Meier method used to assess time to biochemical recurrence.
Measure:Quality of Life
Time Frame:3 to 5 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

November 4, 2019