Prostate CancerEarly Phase 1NCT03734653
Testosterone Therapy in Castration Resistant Prostate Cancer
A Early Phase 1 study testing Transdermal Testosterone in people with Prostate Cancer and Castration-Resistant Prostate Cancer, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, men only
- Conditions the study is for
- Prostate Cancer, Castration-Resistant Prostate Cancer
- What is being tested?
- Transdermal Testosterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2019to 30 Sep 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision to sign and date the consent form
- Male and age > or = 18 years old
- 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 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
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- Serum testosterone level <50ng/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 >1ng/mL
- Soft tissue progression on CT or 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.
- 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
- 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
Who cannot join
- 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
- NYHA class 3 or 4 congestive heart failure
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- 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
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80045
About this study
Official title: Square Wave Testosterone Therapy in Castration Resistant Prostate Cancer
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.
Read the 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.
- Being tested
- Transdermal Testosterone, Standard of Care, Enzalutamide
- Keywords
- Square Wave Testosterone Therapy, Androgen Deprivation Therapy, Transdermal Testosterone, Feasibility Study
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transdermal TestosteroneDrug
Patients will be prescribed 2 packets of testosterone gel 1% containing 50mg per packet to apply transdermally daily.
Standard of Care, EnzalutamideDrug
Patients will take four 40mg capsules of enzalutamide for a total daily dose of 160mg.
| Study group | Role | What they receive |
|---|---|---|
| Square Wave Testosterone Therapy + SOC | Experimental | All patients will receive transdermal testosterone. All patients will also receive standard of care enzalutamide. Patients will alternate between the two therapies. Receives: Drug: Transdermal Testosterone; Drug: Standard of Care, Enzalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of the Administration of Transdermal Testosterone Alternating with Enzalutamide
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.
Measured: Study start date to study end date, up to 12 months, or until patient death
Secondary outcomes (20)
Safety of the Administration of Transdermal Testosterone Alternating with Enzalutamide
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
Measured: Study start date to study end date, up to 12 months, or until patient death
Prostate Specific Antigen (PSA) Response Rate
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.
Measured: Study start date to study end date, up to 12 months, or until patient death
Time to Radiographic Progression
Time to radiographic progression as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: Study start date to study end date, up to 12 months, or until patient death
Time to Radiographic Progression
Time to radiographic progression as measured by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) imaging criteria.
Measured: Study start date to study end date, up to 12 months, or until patient death
Time to PSA Progression
This will be defined by the PCWG3.
Measured: Study start date to study end date, every four weeks, up to 12 months, or until patient death
Maximum Decrease in PSA
PSA will be assessed at baseline and every four weeks. Maximum decrease assessed through these measurements.
Measured: Study start date to study end date, up to 12 months, or until patient death
Physical Function Change
Assessed through handgrip exercises.
Measured: Study start date to study end date, up to 12 months, or until patient death
Physical Function Change
Assessed through chair rise exercises.
Measured: Study start date to study end date, up to 12 months, or until patient death
Patient Activation
Assessed using the Self-Efficacy for Physical Activity Scale (SEPA), which uses a 5 point Likert scale.
Measured: Study start date to study end date, up to 12 months, or until patient death
Reported Fatigue
Measured by the Functional Assessment of Cancer Therapy-Fatigue (FACT-Fatigue 13).
Measured: Study start date to study end date, up to 12 months, or until patient death
Patient Mood and Depression Evaluation
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."
Measured: Study start date to study end date, up to 12 months, or until patient death
Bone Health
Standard bone densometry assessment will be used to calculate T and Z score to determine normal, osteopenic, or osteoporotic bone mineral density.
Measured: Study start date to study end date, up to 12 months, or until patient death
Body Composition
Measured by a DXA scanner. Free fat mass and lean body mass will be assessed to determine sarcopenic obesity.
Measured: Study start date to study end date, up to 12 months, or until patient death
Quality of Life Assessment
Measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P).
Measured: Study start date to study end date, up to 12 months, or until patient death
Change in Hormones
Change in testosterone, estrogen, and sex hormone binding globulin.
Measured: Study start date to study end date, up to 12 months, or until patient death
Self-Reported Physical Function
Measured by the PROMIS-PA.
Measured: Study start date to study end date, up to 12 months, or until patient death
Energy Expenditure
Measured by hood assessment.
Measured: Study start date to study end date, up to 12 months, or until patient death
Change in Max Repetition
Measured by subject's maximal leg press over time in the energy-balance laboratory.
Measured: Study start date to study end date, up to 12 months, or until patient death
Change in Spontaneous Physical Activity and Sedentary Time
Measured through accelerometry. Patients will wear an accelerometer for one week at initiation and again one month later.
Measured: Study start date to study end date, up to 12 months, or until patient death
PSA Response in this Cohort of Patients vs Historical Cohorts
Assessed through IM testosterone historical data.
Measured: Study start date to study end date, up to 12 months, or until patient death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2018
- Study start18 Jan 2019
- Primary completion14 Aug 2024
- Study completion30 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a longitudinal pilot, single arm, interventional study.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer League of Colorado
- Responsible party
- Sponsor
- Investigators
- Laura Graham, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03734653
- Sponsor's protocol ID
- 18-0821.cc
- Status last verified
- Nov 2025
- First submitted
- 6 Nov 2018
- Last updated
- 6 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The deidentified participant data will be shared after any study publication (between 6 and 36 months post publication). Study protocol also available.
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Square Wave Testosterone Therapy in Castration Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT03734653
- Acronym / sponsor ID
- 18-0821.cc
- Keywords
- Square Wave Testosterone Therapy, Androgen Deprivation Therapy, Transdermal Testosterone, Feasibility Study
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Cancer League of Colorado
- Study start
- 18 Jan 2019 (actual)
- Primary completion
- 14 Aug 2024 (actual)
- Study completion
- 30 Sep 2025 (actual)
- First posted
- 8 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a longitudinal pilot, single arm, interventional study.
| Arm | Type | Receives |
|---|---|---|
| Square Wave Testosterone Therapy + SOC | Experimental | Drug: Transdermal Testosterone, Drug: Standard of Care, EnzalutamideAll patients will receive transdermal testosterone. All patients will also receive standard of care enzalutamide. Patients will alternate between the two therapies. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Provision to sign and date the consent form
- Male and age > or = 18 years old
- 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 ADT for prostate cancer with a GnRH analogue/antagonist or bilateral orchiectomy for at least 6 months prior to day 1
Key exclusion criteria (17 listed)
- 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:
- Previous exposure to a second-generation anti-androgen i.e enzalutamide or apalutamide
- Received investigational agent within 2 weeks of screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transdermal TestosteronePatients will be prescribed 2 packets of testosterone gel 1% containing 50mg per packet to apply transdermally daily. | Drug | Square Wave Testosterone Therapy + SOC |
| Standard of Care, EnzalutamidePatients will take four 40mg capsules of enzalutamide for a total daily dose of 160mg. | Drug | Square Wave Testosterone Therapy + SOC |
Primary outcome
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.
20 secondary outcomes
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
Prostate Specific Antigen (PSA) Response Rate
Time frame: Study start date to study end date, up to 12 months, or until patient death
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
Time frame: Study start date to study end date, up to 12 months, or until patient death
Time to PSA Progression
Time frame: Study start date to study end date, every four weeks, up to 12 months, or until patient death
Maximum Decrease in PSA
Time frame: Study start date to study end date, up to 12 months, or until patient death
Physical Function Change
Time frame: Study start date to study end date, up to 12 months, or until patient death
Physical Function Change
Time frame: Study start date to study end date, up to 12 months, or until patient death
Patient Activation
Time frame: Study start date to study end date, up to 12 months, or until patient death
Reported Fatigue
Time frame: Study start date to study end date, up to 12 months, or until patient death
Patient Mood and Depression Evaluation
Time frame: Study start date to study end date, up to 12 months, or until patient death
Bone Health
Time frame: Study start date to study end date, up to 12 months, or until patient death
Body Composition
Time frame: Study start date to study end date, up to 12 months, or until patient death
Quality of Life Assessment
Time frame: Study start date to study end date, up to 12 months, or until patient death
Change in Hormones
Time frame: Study start date to study end date, up to 12 months, or until patient death
Self-Reported Physical Function
Time frame: Study start date to study end date, up to 12 months, or until patient death
Energy Expenditure
Time frame: Study start date to study end date, up to 12 months, or until patient death
Change in Max Repetition
Time frame: Study start date to study end date, up to 12 months, or until patient death
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2025.
- Individual participant dataSharing planned: Yes. The deidentified participant data will be shared after any study publication (between 6 and 36 months post publication). Study protocol also available.
Related trials for Prostate Cancer
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The COSMYC Trial (COmbined Suppression of MYC)
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Not yet recruitingPhase 3
A Study of JNJ-101556143 With Best Supportive Care in Participants With Metastatic Prostate Cancer
Prostatic Neoplasms
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
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RecruitingObservational study
PULSE Registry: for Patients Receiving Lutetium (177Lu) Vipivotide Tetraxetan
Metastatic Prostate Cancer
RecruitingPhase 2
Relugolix and Enzalutamide in Combination With Radiation Therapy for the Treatment of Very High Risk Prostate Cancer, OPTIMAL Trial
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura Graham, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Transdermal Testosterone in people with Prostate Cancer and Castration-Resistant Prostate Cancer, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2025.