Clinical trial NCT03734653: Testosterone Therapy in Castration Resistant Prostate Cancer
Official title: Square Wave Testosterone Therapy in Castration Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Prostate Cancer
Castration-Resistant Prostate Cancer
Keywords: Square Wave Testosterone Therapy
Androgen Deprivation Therapy
Transdermal Testosterone
Feasibility Study
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Cancer League of Colorado
First posted: 2018-11-08
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a longitudinal pilot, single arm, interventional study.
Primary purpose: TREATMENT

Brief summary: This is an open-labeled, single-arm, interventional pilot study. It is being done to determine the feasibility of the administration of transdermal testosterone alternating with enzalutamide, as well as the safety and efficacy.

Detailed description: The primary endpoint of this trial is to determine the feasibility of the administration of transdermal testosterone alternating with enzalutamide. High dose testosterone has shown activity in phase II studies of patients with castration resistant metastatic prostate cancer; however, these studies have generally employed the intramuscular formulation. It has been hypothesized that the transdermal formulation will show activity but will have less potential for toxicity due to extremely high levels of circulating testosterone (i.e. thrombotic events). In addition, this will allow for a steady state of elevated testosterone, rather than the peaks and troughs seen with the IM approach.

Eligibility criteria: Inclusion Criteria:

1. Provision to sign and date the consent form
2. Male and age \> or = 18 years old
3. Stated willingness to comply with all study procedures and be available for the duration of the study
4. Histologically or cytologically proven adenocarcinoma of the prostate
5. Ongoing ADT for prostate cancer with a GnRH analogue/antagonist or bilateral orchiectomy for at least 6 months prior to day 1
6. 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
7. Serum testosterone level \<50ng/dL at the screening visit
8. 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 \>1ng/mL
   * Soft tissue progression on CT or MRI based on RECIST 1.1 criteria or progression of bone disease according to PCWG3 criteria
9. 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.
10. Acceptable Clinical laboratory values at Screening Visit which include:

    * Absolute neutrophil count ≥ 1000/uL; platelet count ≥ 100,000/uL, hemoglobin ≥ 8g/dL
    * Total bilirubin ≤ 1.5xULN (unless documented Gilbert's); alanine aminotransferase or aspartate aminotransferase ≤ 2.5xULN
    * Creatinine ≤ 2mg/dL
    * Hemoglobin ≤ 17.5 g/dL
11. 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
12. Must use a condom if having sex with a pregnant woman
13. 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
14. Patients may have received any number of lines of therapy for castration resistant disease

Exclusion Criteria:

1. 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
2. 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
3. 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
   * 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 HTN (systolic \>180mmHg or diastolic \>105mmHg at screening
4. Previous exposure to a second-generation anti-androgen i.e enzalutamide or apalutamide
5. Received investigational agent within 2 weeks of screening
6. Therapy with antineoplastic systemic chemotherapy or biological therapy within 2 weeks of screening
7. Radiation therapy within 2 weeks of screening
8. 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
9. History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agent
10. Known or suspected brain metastasis or active leptomeningeal disease
11. 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
12. 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

Primary outcomes:
measure: Feasibility of the Administration of Transdermal Testosterone Alternating with Enzalutamide
timeFrame: Study start date to study end date, up to 12 months, or until patient death
Secondary outcomes:
measure: Safety of the Administration of Transdermal Testosterone Alternating with Enzalutamide
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Prostate Specific Antigen (PSA) Response Rate
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Time to Radiographic Progression
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Time to Radiographic Progression
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Time to PSA Progression
timeFrame: Study start date to study end date, every four weeks, up to 12 months, or until patient death
measure: Maximum Decrease in PSA
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Physical Function Change
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Physical Function Change
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Patient Activation
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Reported Fatigue
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Patient Mood and Depression Evaluation
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Bone Health
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Body Composition
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Quality of Life Assessment
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Change in Hormones
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Self-Reported Physical Function
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Energy Expenditure
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Change in Max Repetition
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: Change in Spontaneous Physical Activity and Sedentary Time
timeFrame: Study start date to study end date, up to 12 months, or until patient death
measure: PSA Response in this Cohort of Patients vs Historical Cohorts
timeFrame: Study start date to study end date, up to 12 months, or until patient death
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Laura Graham, MD
role: PRINCIPAL_INVESTIGATOR
References: