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Apalutamide and Leuprolide Acetate in Treating Patients with Prostate Cancer before Surgery

Trial Status: Active

This phase II trial studies how well apalutamide and leuprolide acetate work in treating patients with prostate cancer before surgery. Hormone therapy using apalutamide and leuprolide acetate may fight prostate cancer by lowering the amount of androgen the body makes and / or blocking the use of androgen by the tumor cells.

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, or PSA >= 10, and >= T2b, for whom radical prostatectomy has been recommended and who choose to undergo radical prostatectomy
  • A minimum tissue requirement of >= 1 core biopsies with tumor involvement
  • 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 >= 100 k/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 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x 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, PCSPES (or PC-x product), megestrol acetate, or estrogen containing nutraceuticals 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)
  • 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
  • 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
  • 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


Case Comprehensive Cancer Center
Status: ACTIVE
Contact: Moshe C. Ornstein
Phone: 216-445-6592


I. To evaluate the differential effect of neo-adjuvant leuprolide acetate (leuprolide) and apalutamide on dihydrotestosterone (DHT) concentration in benign prostate tissue based on HSD3B1 genotype.


I. To evaluate the differential effect of neoadjuvant leuprolide and ARN-509 on other androgen (testosterone [T], dehydroepiandrosterone [DHEA], androstenediol, 5 alpha-androstanedione [5 alpha-dione], androstenedione [AD], androsterone and 5 alpha-androstanediol) concentrations in benign and malignant prostate tissue based on HSD3B1 genotype.

II. To compare the level of DHT, T, DHEA, androstenediol, 5 alpha-dione, AD, androsterone and 5 alpha-androstanediol between normal and malignant prostate tissue after neoadjuvant treatment with leuprolide and apalutamide.

III. To determine the safety of the combination of leuprolide and apalutamide administered prior to radical prostatectomy.

IV. To evaluate prostate-specific antigen (PSA), FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via immunohistochemistry [IHC] and quantitative polymerase chain reaction [qPCR]) in benign and malignant prostate tissue after treatment with leuprolide and apalutamide.


Patients receive leuprolide acetate intramuscularly (IM) once on day -28 and apalutamide orally (PO) starting on day -28 until radical prostatectomy in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up for 28 days.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Moshe C. Ornstein

  • Primary ID CASE5815
  • Secondary IDs NCI-2016-01612
  • ID NCT02770391