Apalutamide and Leuprolide in Intermediate and High-risk Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Leuprolide acetate; Apalutamide; Radical prostatectomy
Intervention description: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3; Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Intervention MeSH terms: Leuprolide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HSD3B1 Genotype; Steroid Metabolism; High-risk Prostate Cancer; Apalutamide; ARN-509

Summary:

      This is a research study to test an investigational drug (Not FDA approved), Apalutamide
      given in combination with Leuprolide acetate (FDA approved) in men diagnosed with high-risk
      prostate cancer who have already selected to have surgery to remove their prostate gland as
      part of their treatment plan. The main purpose of this study is to determine how tumors make
      androgens (male hormones), which makes these tumors more aggressive and resistant to hormonal
      therapy and how a short period of treatment with Apalutamide and leuprolide acetate prior to
      surgery can affect the production of these hormones in normal and malignant prostate tissue.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adenocarcinoma of the prostate with histological or cytological confirmation without
             neuroendocrine differentiation or small cell histology and with G 4+3 or higher, and
             PSA ≥ 10, and ≥T2b, for whom radical prostatectomy has been recommended and who choose
             to undergo radical prostatectomy.

          -  A minimum tissue requirement of ≥3 core biopsies with tumor involvement and at least
             50% tumor involvement in one of the core biopsies is required.

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Hemoglobin of ≥ 10 g/dL, independent of transfusion and/or growth factors within 3
             months prior to randomization

          -  Platelet count of ≥ 100k/mL independent of transfusion and/or growth factors within 3
             months prior to randomization

          -  Serum albumin ≥3.0 g/dL

          -  Serum creatinine < 2.0 times the upper limit of normal (ULN) {or a calculated
             creatinine clearance ≥ 60 mL/min}

          -  Serum potassium ≥3.5 mmol/L

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN

          -  Total serum bilirubin levels < 1.5 x ULN (Note: In subjects with Gilbert's syndrome,
             if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct
             bilirubin is ≤1.5 × ULN, subject may be eligible)

          -  Be capable of swallowing study agents whole as a tablet

          -  Be willing/able to adhere to the prohibitions and restrictions specified in this
             protocol

          -  Have signed an informed consent document indicating that the subject understands the
             purpose of and procedures required for the study and are willing to participate in the
             study.

          -  Medications known to lower the seizure threshold must be discontinued or substituted
             at least 4 weeks prior to study entry.

          -  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 following the last dose of study drug.

        Exclusion Criteria:

          -  The use of any prior hormones including luteinizing hormone-releasing hormone (LHRH)
             agonists , LHRH antagonists, antiandrogens such as bicalutamide, flutamide and
             nilutamide, and/or the use of 5-alpha reductase inhibitors, prostate cancer (PC) Spes
             (or PC-x product), Megestrol Acetate, or estrogen containing nutriceuticals within 6
             months of study treatment initiation.

          -  Prior radiation therapy, immunotherapy, chemotherapy or other investigational therapy
             given for prostate cancer.

          -  "Currently active" second malignancy other than non-melanoma skin cancers or
             non-muscle invasive transitional cell carcinoma of bladder. Patients are not
             considered to have a "currently active" malignancy if they have completed therapy and
             are now considered (by their physician) to be at less than 30% risk for relapse.

          -  History of seizure or condition that may pre-dispose to seizure (including but not
             limited to prior stroke, transient ischemic attack, loss of consciousness within 1
             year prior to randomization, brain arteriovenous malformation; or intracranial masses
             such as schwannomas and meningiomas that are causing edema or mass effect)

          -  Current systemic steroid therapy (inhaled or topical steroids are also not allowed)

          -  Have received treatment with any form of therapy with CYP17 inhibitory activity such
             as ketoconazole, aminoglutethimide, or an antiandrogen such as bicalutamide within 6
             months of study treatment initiation.

          -  Use of herbal products that may have hormonal anti-prostate cancer activity and/or are
             known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids within 6
             months of enrollment

          -  Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)

          -  Have uncontrolled hypertension;subjects with a history of hypertension are permitted
             in the study provided their blood pressure is controlled by anti-hypertensive therapy,
             at the discretion of the treating physician

          -  Have a known history of pituitary or adrenal dysfunction

          -  Have clinically significant heart disease as evidenced by severe or unstable angina,
             myocardial infarction, symptomatic congestive heart failure, arterial or venous
             thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including
             transient ischemic attacks), or clinically significant ventricular arrhythmias within
             6 months prior to randomization

          -  Have a history of gastric bypass surgery or severe malabsorption that may interfere
             with the absorption of the study agents

          -  Be taking or require the use of prohibited medications as listed

          -  Have any condition that, in the opinion of the investigator, would compromise the
             well-being of the subject or the study or prevent the subject from meeting or
             performing study requirements