Clinical Trials /

Testosterone Therapy in Castration Resistant Prostate Cancer

NCT03734653

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Testosterone Therapy in Castration Resistant Prostate Cancer
  • Official Title: Square Wave Testosterone Therapy in Castration Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-0821.cc
  • SECONDARY ID: P30CA046934
  • NCT ID: NCT03734653

Conditions

  • Prostate Cancer
  • Castration-Resistant Prostate Cancer

Interventions

DrugSynonymsArms
Transdermal TestosteroneSquare Wave Testosterone Therapy + SOC
Standard of Care, EnzalutamideSquare Wave Testosterone Therapy + SOC

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Square Wave Testosterone Therapy + SOCExperimentalAll patients will receive transdermal testosterone. All patients will also receive standard of care enzalutamide. Patients will alternate between the two therapies.
  • Transdermal Testosterone
  • Standard of Care, Enzalutamide

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
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of the Administration of Transdermal Testosterone Alternating with Enzalutamide
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:This study will be considered feasible if at least 50% of patients approached for participation enroll and if at least 50% of patients that initiate therapy do not withdraw consent for participation.

Secondary Outcome Measures

Measure:Safety of the Administration of Transdermal Testosterone Alternating with Enzalutamide
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Safety will be assessed based on the Common Terminology Criteria of Adverse Events (CTCAE) v5.0 criteria, in which rates of Grade 1-5 AE will be assessed, with a prticular attention to grade 3-5 events
Measure:Prostate Specific Antigen (PSA) Response Rate
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:PSA response rates as measured by serum PSA at designated study visits. Response will be defined as a decline in the serum PSA of 50% from baseline value at start of study.
Measure:Time to Radiographic Progression
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Time to radiographic progression as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
Measure:Time to Radiographic Progression
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Time to radiographic progression as measured by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) imaging criteria.
Measure:Time to PSA Progression
Time Frame:Study start date to study end date, every four weeks, up to 12 months, or until patient death
Safety Issue:
Description:This will be defined by the PCWG3.
Measure:Maximum Decrease in PSA
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:PSA will be assessed at baseline and every four weeks. Maximum decrease assessed through these measurements.
Measure:Physical Function Change
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Assessed through handgrip exercises.
Measure:Physical Function Change
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Assessed through chair rise exercises.
Measure:Patient Activation
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Assessed using the Self-Efficacy for Physical Activity Scale (SEPA), which uses a 5 point Likert scale.
Measure:Reported Fatigue
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Measured by the Functional Assessment of Cancer Therapy-Fatigue (FACT-Fatigue 13).
Measure:Patient Mood and Depression Evaluation
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Measured through the Center for Epidemiologic Studies-Depression Scale (CES-D), which uses a point system based on responses ranging from "not at all" to "all the time."
Measure:Bone Health
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Standard bone densometry assessment will be used to calculate T and Z score to determine normal, osteopenic, or osteoporotic bone mineral density.
Measure:Body Composition
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Measured by a DXA scanner. Free fat mass and lean body mass will be assessed to determine sarcopenic obesity.
Measure:Quality of Life Assessment
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P).
Measure:Change in Hormones
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Change in testosterone, estrogen, and sex hormone binding globulin.
Measure:Self-Reported Physical Function
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Measured by the PROMIS-PA.
Measure:Energy Expenditure
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Measured by hood assessment.
Measure:Change in Max Repetition
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Measured by subject's maximal leg press over time in the energy-balance laboratory.
Measure:Change in Spontaneous Physical Activity and Sedentary Time
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Measured through accelerometry. Patients will wear an accelerometer for one week at initiation and again one month later.
Measure:PSA Response in this Cohort of Patients vs Historical Cohorts
Time Frame:Study start date to study end date, up to 12 months, or until patient death
Safety Issue:
Description:Assessed through IM testosterone historical data.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Trial Keywords

  • Square Wave Testosterone Therapy
  • Androgen Deprivation Therapy
  • Transdermal Testosterone
  • Feasibility Study

Last Updated

June 28, 2019