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Transdermal Testosterone and Enzalutamide in Treating Patents with Castration Resistant Prostate Cancer Receiving Androgen Deprivation Therapy

Trial Status: Active

This early phase I trial studies how well testosterone works when delivered through the skin and is used alternately with enzalutamide in treating patients with castration-resistant prostate cancer who are receiving androgen deprivation therapy. Hormone therapy using testosterone may help to maintain the amount of testosterone in the body, and enzalutamide may help to reduce the prostate specific antigen level. Giving transdermal testosterone alternately with enzalutamide may work better in treating patients with castration resistant prostate cancer.

Inclusion Criteria

  • Provision to sign and date the consent form.
  • Stated willingness to comply with all study procedures and be available for the duration of the study.
  • Histologically or cytologically proven adenocarcinoma of the prostate.
  • Ongoing antiandrogen therapy (ADT) for prostate cancer with a GnRH analogue/antagonist or bilateral orchiectomy for at least 6 months prior to day 1.
  • Patients on a first generation anti-androgen (e.g. bicalutamide, flutamide, nilutamide) must have at least a 6-week washout prior to randomization and must show continued PSA progression.
  • Serum testosterone level < 50 ng/dL at the screening visit.
  • Progressive disease at screening as defined by one or more of the following criteria: * PSA progression: minimum of 2 rising values within an interval of > 1 week between values. And a value at screening of > 1 ng/mL * Soft tissue progression on computed tomography (CT) or magnetic resonance imaging (MRI) based on RECIST 1.1 criteria or progression of bone disease according to PCWG3 criteria.
  • Patients worst pain in the last 24 hours must rank less than 4 on a 0-10 scale and patients cannot be on daily narcotic medications to treat cancer-related pain. This assessment must occur within the screening window and be documented in the patient’s medical record
  • Absolute neutrophil count >= 1000/uL (at screening).
  • Platelet count >= 100,000/uL (at screening).
  • Hemoglobin >= 8 g/dL (at screening).
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless documented Gilbert’s) (at screening).
  • Alanine aminotransferase or aspartate aminotransferase =< 2.5 x ULN (at screening).
  • Creatinine =< 2 mg/dL (at screening).
  • Hemoglobin =< 17.5 g/dL (at screening).
  • Evidence of metastatic disease at any time point on axial imaging or bone scan, or previous biopsy. Stage IV pelvic lymph node involvement is acceptable.
  • Must use a condom if having sex with a pregnant woman.
  • A male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration.
  • Patients may have received any number of lines of therapy for castration resistant disease.

Exclusion Criteria

  • Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement that is well documented to be due to prostate cancer or benign prostatic hyperplasia.
  • Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone due to a potential tumor flare (e.g. high-risk bone lesions which may result in fracture or spinal cord compression.
  • Clinically significant cardiovascular disease as evidenced by any of the following: * Myocardial infarction with 6 months of screening * Uncontrolled angina within 3 months of screening * New York Heart Association (NYHA) class 3 or 4 congestive heart failure * Clinically significant ventricular arrhythmia * Mobitz II/second degree/or 3rd degree heart block without a pacemaker in place; uncontrolled hypertension (HTN) (systolic >180 mmHg or diastolic >105 mmHg at screening.
  • Previous exposure to a second-generation anti-androgen i.e enzalutamide or apalutamide.
  • Received investigational agent within 2 weeks of screening.
  • Therapy with antineoplastic systemic chemotherapy or biological therapy within 2 weeks of screening.
  • Radiation therapy within 2 weeks of screening.
  • History of a prior malignancy (excluding an adequately treated basal or squamous cell skin cancer, superficial bladder cancer, or a cancer in situ) within 5 years prior to study enrollment.
  • History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agent.
  • Known or suspected brain metastasis or active leptomeningeal disease.
  • History of seizure at any time in the past. Also, history of loss of consciousness or transient ischemic attack within 12 months of Day 1 visit.
  • 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.

Colorado

Aurora
University of Colorado Hospital
Status: ACTIVE
Contact: Elizabeth Riley Kessler
Phone: 720-848-0170

PRIMARY OBJECTIVES:

I. Feasibility of the administration of transdermal testosterone alternating with enzalutamide.

SECONDARY OBJECTIVES:

I. To determine the prostate-specific antigen (PSA) response rate.

II. To measure time to radiographic progression as measured by Response Evaluation Criteria in Solid Tumors (RECIST) and Prostate Cancer Working Group (PCWG3) imaging criteria.

III. To measure time to PSA progression.

IV. To measure maximum decrease in PSA.

V. To measure safety via frequency and severity of adverse events through Common Terminology Criteria for Adverse Events (CTCAE) grading criteria.

VI. To assess physical function change through hand grip and chair rise assessments.

VII. To assess patient activation using the SEPA.

VIII. To assess Reported fatigue as measured by the Functional Assessment of Cancer Therapy-Fatigue (FACT-F).

IX. To assess Bone health, as measured by a dual-energy X-ray absorptiometry (DXA) scanner.

X. To assess Body composition (sarcopenic obesity), as measured by a DXA scanner.

XI. To assess quality of life (QOL), as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P).

XII. To assess Change in testosterone, estrogen and sex hormone binding globulin.

XIII. To assess self-reported physical function by the Patient-Reported Outcomes Measurement Information System-Patient Activity (PROMIS-PA).

XIV. To assess Energy expenditure as measured by hood assessment (subset).

XV. To assess Change in Max Repetition - muscle strength – through max rep testing in bench press and leg press (subset).

XVI. To assess Change in spontaneous physical activity and sedentary time through accelerometry (subset).

XVII. To compare PSA response in this cohort of patients in comparison to historical patients that have received intramuscular testosterone.

OUTLINE:

Patients receive testosterone transdermally daily and may alternate to enzalutamide orally (PO) once daily (QD). Alternation between therapies may be up to 2 rounds of testosterone. Treatment continuous for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days and then every 3 months for 1 year.

Trial Phase Phase O

Trial Type Treatment

Lead Organization
University of Colorado Hospital

Principal Investigator
Elizabeth Riley Kessler

  • Primary ID 18-0821
  • Secondary IDs NCI-2018-03756
  • Clinicaltrials.gov ID NCT03734653