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Testosterone Therapy in Castration Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03734653
Recruitment Status : Active, not recruiting
First Posted : November 8, 2018
Last Update Posted : May 13, 2022
Sponsor:
Collaborator:
Cancer League of Colorado
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE November 6, 2018
First Posted Date  ICMJE November 8, 2018
Last Update Posted Date May 13, 2022
Actual Study Start Date  ICMJE January 18, 2019
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2018)
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 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2019)
  • 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 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
  • Prostate Specific Antigen (PSA) Response Rate [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    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.
  • Time to Radiographic Progression [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Time to radiographic progression as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
  • Time to Radiographic Progression [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Time to radiographic progression as measured by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) imaging criteria.
  • Time to PSA Progression [ Time Frame: Study start date to study end date, every four weeks, up to 12 months, or until patient death ]
    This will be defined by the PCWG3.
  • Maximum Decrease in PSA [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    PSA will be assessed at baseline and every four weeks. Maximum decrease assessed through these measurements.
  • Physical Function Change [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Assessed through handgrip exercises.
  • Physical Function Change [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Assessed through chair rise exercises.
  • Patient Activation [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Assessed using the Self-Efficacy for Physical Activity Scale (SEPA), which uses a 5 point Likert scale.
  • Reported Fatigue [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by the Functional Assessment of Cancer Therapy-Fatigue (FACT-Fatigue 13).
  • Patient Mood and Depression Evaluation [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    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."
  • Bone Health [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Standard bone densometry assessment will be used to calculate T and Z score to determine normal, osteopenic, or osteoporotic bone mineral density.
  • Body Composition [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by a DXA scanner. Free fat mass and lean body mass will be assessed to determine sarcopenic obesity.
  • Quality of Life Assessment [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P).
  • Change in Hormones [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Change in testosterone, estrogen, and sex hormone binding globulin.
  • Self-Reported Physical Function [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by the PROMIS-PA.
  • Energy Expenditure [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by hood assessment.
  • Change in Max Repetition [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by subject's maximal leg press over time in the energy-balance laboratory.
  • 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 ]
    Measured through accelerometry. Patients will wear an accelerometer for one week at initiation and again one month later.
  • 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 ]
    Assessed through IM testosterone historical data.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2018)
  • 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 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
  • Prostate Specific Antigen (PSA) Response Rate [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    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.
  • Time to Radiographic Progression [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Time to radiographic progression as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
  • Time to Radiographic Progression [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Time to radiographic progression as measured by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) imaging criteria.
  • Time to PSA Progression [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    This will be defined by the PCWG3.
  • Maximum Decrease in PSA [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    PSA will be assessed at baseline and every four weeks. Maximum decrease assessed through these measurements.
  • Physical Function Change [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Assessed through handgrip exercises.
  • Physical Function Change [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Assessed through chair rise exercises.
  • Patient Activation [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Assessed using the Self-Efficacy for Physical Activity scale (SEPA).
  • Reported Fatigue [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by the Functional Assessment of Cancer Therapy-Fatigue (FACT-Fatigue 13).
  • Patient Mood and Depression Evaluation [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured through the Center for Epidemiologic Studies-Depression Scale (CES-D)
  • Bone Health [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Standard bone densometry assessment will be used to calculate T and Z score to determine normal, osteopenic, or osteoporotic bone mineral density.
  • Body Composition [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by a DXA scanner. Free fat mass and lean body mass will be assessed to determine sarcopenic obesity.
  • Quality of Life Asssessment [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P).
  • Change in Hormones [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Change in testosterone, estrogen, and sex hormone binding globulin.
  • Self-Reported Physical Function [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by the PROMIS-PA.
  • Energy Expenditure [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by hood assessment.
  • Change in Max Repetition [ Time Frame: Study start date to study end date, up to 12 months, or until patient death ]
    Measured by subject's maximal leg press over time in the energy-balance laboratory.
  • 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 ]
    Measured through accelerometry. Patients will wear an accelerometer for one week at initiation and again one month later.
  • 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 ]
    Assessed through IM testosterone historical data.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Testosterone Therapy in Castration Resistant Prostate Cancer
Official Title  ICMJE Square Wave Testosterone Therapy in Castration Resistant Prostate Cancer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a longitudinal pilot, single arm, interventional study.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostate Cancer
  • Castration-Resistant Prostate Cancer
Intervention  ICMJE
  • Drug: Transdermal Testosterone
    Patients will be prescribed 2 packets of testosterone gel 1% containing 50mg per packet to apply transdermally daily.
  • Drug: Standard of Care, Enzalutamide
    Patients will take four 40mg capsules of enzalutamide for a total daily dose of 160mg.
Study Arms  ICMJE Experimental: Square Wave Testosterone Therapy + SOC
All patients will receive transdermal testosterone. All patients will also receive standard of care enzalutamide. Patients will alternate between the two therapies.
Interventions:
  • Drug: Transdermal Testosterone
  • Drug: Standard of Care, Enzalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 26, 2021)
15
Original Estimated Enrollment  ICMJE
 (submitted: November 6, 2018)
50
Estimated Study Completion Date  ICMJE August 2025
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03734653
Other Study ID Numbers  ICMJE 18-0821.cc
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The deidentified participant data will be shared after any study publication (between 6 and 36 months post publication). Study protocol also available.
Supporting Materials: Study Protocol
Time Frame: Between 6 and 36 months post publication
Access Criteria: Sound proposal with IRB approval. Analyses can be be in keeping with the submitted protocol. This will be reviewed internally for use.
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Cancer League of Colorado
Investigators  ICMJE
Principal Investigator: Elizabeth Kessler, MD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP