Testosterone Therapy in Castration Resistant Prostate Cancer

NCT ID: NCT03734653

Last Updated: 2025-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-18
• Study Completion Date: 2025-09-30

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.

Conditions

Prostate Cancer; Castration-Resistant Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Transdermal Testosterone

Intervention Type: DRUG

Patients will be prescribed 2 packets of testosterone gel 1% containing 50mg per packet to apply transdermally daily.

Standard of Care, Enzalutamide

Intervention Type: DRUG

Patients will take four 40mg capsules of enzalutamide for a total daily dose of 160mg.

Interventions

Transdermal Testosterone

Patients will be prescribed 2 packets of testosterone gel 1% containing 50mg per packet to apply transdermally daily.

Intervention Type: DRUG

Standard of Care, Enzalutamide

Patients will take four 40mg capsules of enzalutamide for a total daily dose of 160mg.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Cancer League of Colorado

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laura Graham, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Hospital

Aurora, Colorado, United States

Countries

United States

Other Identifiers

18-0821.cc

Identifier Type: -

Identifier Source: org_study_id