Maintaining Suppression of Testosterone With Transdermal Estradiol Gel (MASTERS)

March 8, 2022 updated by: BHR Pharma, LLC

A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study of BHR-200 (0.36% Transdermal Estradiol Gel) for the Maintenance of Testosterone Suppression in Men With Advanced Androgen-Sensitive Prostate Cancer

The objective of this clinical study is to evaluate the safety and efficacy of three different doses of BHR-200 (0.36% transdermal estradiol gel) compared to placebo for the maintenance of testosterone (T) suppression in men with advanced androgen-sensitive prostate cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a multi-center, randomized, double-blind, placebo-controlled, dose finding study in men with advanced androgen-sensitive prostate cancer. Patients who give informed consent will have screening evaluations, and if fulfilling the entry criteria, will be randomized to one of 4 treatment groups: 1mL, 2mL or 3mL of 0.36% BHR-200 (transdermal estradiol gel) or Placebo. Study drug will be initiated on the day they were scheduled to receive next depot GnRH agonist injection. Patients will be offered low-dose radiation to aid in the prevention of gynecomastia. Patients will apply the study drug once per day. The first dose of study gel will be applied under the supervision of the PI/designee. Subsequent doses will be self-administered daily by the patient until he is no longer chemically castrated (testosterone levels increase above 50 ng/dL), a rise over baseline PSA of > 0.5 ng/mL is observed, or he has completed 52 weeks of study drug administration. At the conclusion of study participation, patients will be advised to resume standard of care treatment under the supervision of their healthcare provider. While on treatment, patients will be evaluated at Day 1 and every 2 weeks, for the first 24 weeks and every 4 weeks thereafter with a final post-treatment follow-up visit 2 weeks (+/- 1 week) post last dose administration.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
34

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85741
        • Urological Associates of Southern Arizona
    • Florida
      • Aventura, Florida, United States, 33180
        • South Florida Medical Research
      • Daytona Beach, Florida, United States, 32114
        • Advanced Urology Institute
    • Iowa
      • Council Bluffs, Iowa, United States, 51501
        • Adult Pediatric Urology, PC
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Adult Pediatric Urology, PC
    • New Jersey
      • Voorhees, New Jersey, United States, 08043
        • Delaware Valley Urology
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • AccumetRX Clinical Trials
    • New York
      • Syracuse, New York, United States, 13210
        • Associated Medical Professionals of NY (AMP of NY)
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • Eastern Urological Associates
    • Pennsylvania
      • Bala-Cynwyd, Pennsylvania, United States, 19044
        • Urologic Consultants of Southeastern Pennsylvania (UCSEPA)
    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Carolina Urologic Research Center
    • Texas
      • Dallas, Texas, United States, 75231
        • Urology Clinics of North Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. Males, Ages 18 and older
  2. Body Mass Index (BMI) between 18 and 35 kg/m2 (inclusive)
  3. Not currently hospitalized
  4. Clinical indication of adenocarcinoma of the prostate evidenced by a biopsy report on record
  5. At present receiving ADT treatment with a GnRH agonist for at least 2 months but not longer than 36 months without interruption - Note: If the patient received GnRH agonist treatment prior to the treatment described under 5, there must be evidence of a period without GnRH agonist treatment for a minimum of 2 months prior to starting the present treatment as is seen, for example with intermittent treatment regimens.
  6. Able to initiate Screening procedures 2 weeks prior to the next scheduled injection with a GnRH agonist
  7. Willing to discontinue current ADT regimen for the duration of the study
  8. T level less than 50 ng/dL at Screening
  9. WHO/ECOG performance status of 0 or 1
  10. Life expectancy of at least 1 year
  11. Adequate renal function demonstrated by having normal blood urea nitrogen (BUN) and Creatinine Screening lab values

Exclusion Criteria:

  1. History or presence of allergic or adverse response to estradiol
  2. Presence of symptomatic metastatic disease, risk of spinal cord compression or urinary obstruction
  3. History within the past 2 years of deep vein thrombosis (DVT), pulmonary embolism (PE2), a known thrombophilic disorder (eg.protein C, protein S, or antithrombin deficiency), or cerebrovascular accident (CVA)
  4. History within the past 2 years of myocardial infarction or a coronary vascular procedure (e.g. percutaneous coronary intervention, coronary artery bypass graft)
  5. History of congestive heart failure
  6. Use of any investigational drug, biologic, or device within 28 days prior to the first dose of study gel
  7. Use of any of the following known inducers or inhibitors of cytochrome P450 3A4 (CYP3A4): phenobarbital, carbamazepine, rifampin, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, St. John's Wort preparations (Hypericum perforatum), and grapefruit juice
  8. Hematological parameters (Hematocrit or Hemoglobin) outside 20% of the upper or lower limits of normal at Screening
  9. Active skin rash, sunburn, or other skin disorder on the upper arm(s) that requires treatment or may affect skin absorption of study gel
  10. Resting uncontrolled hypertension (HTN) (160/100 mmHg) at Screening
  11. Co-existent malignancy or a history of malignancy during the past 5 years, with the exception of basal and/or squamous cell carcinoma of the skin
  12. Any other significant concurrent illness or disease or condition that in the opinion of the Investigator might interfere with the patient's ability to receive the treatment outlined in the protocol or might put him at additional risk

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: BHR-200 Low Dose
3 mg estradiol per 1 mL 0.36% BHR-200 (transdermal 17β-estradiol gel) applied daily to the skin for up to 52 weeks.
Drug: BHR-200 (0.36% transdermal 17β-estradiol gel)
An absorptive hydroalcoholic gel preparation containing 17β-estradiol.
Other Names:
  • BHR-200
Experimental: BHR-200 Mid Dose
6 mg estradiol per 2 mL 0.36% BHR-200 (transdermal 17β-estradiol gel) applied daily to the skin for up to 52 weeks.
Drug: BHR-200 (0.36% transdermal 17β-estradiol gel)
An absorptive hydroalcoholic gel preparation containing 17β-estradiol.
Other Names:
  • BHR-200
Experimental: BHR-200 High Dose
9 mg estradiol per 3 mL 0.36% BHR-200 (transdermal 17β-estradiol gel) applied daily to the skin for up to 52 weeks.
Drug: BHR-200 (0.36% transdermal 17β-estradiol gel)
An absorptive hydroalcoholic gel preparation containing 17β-estradiol.
Other Names:
  • BHR-200
Placebo Comparator: Placebo
1, 2 or 3 mL of Placebo gel containing 0 mg estradiol applied daily for up to 52 weeks.
Drug: Placebo
An absorptive hydroalcoholic gel preparation gel of the same ingredients as BHR-200, but without 17β-estradiol.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maintenance of Testosterone Suppression at Week 12
Time Frame: Week 12

Primary Efficacy Endpoint was the percentage of patients failing to maintain castrate levels of T (T < 50 ng/dL).

Testosterone suppression, defined as the absence of any T level measurement over 50 ng/dL during Weeks 4 to 12.
Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maintenance of Testosterone Suppression at Week 24
Time Frame: Week 24
Pproportion of patients failing to maintaincastrate levels of T (T < 50 ng/dL). Testosterone suppression, defined as the absence of any T level measurement over 50 ng/dL during Weeks 4 to 24.
Week 24
Number of Patients Reporting Thromboembolic Adverse Events
Time Frame: To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study
Number of patients and severity of thromboembolic adverse events
To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Luteinizing Hormone (LH)
Time Frame: Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Serum concentrations of luteinizing hormone (LH)
Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Sex Hormone Binding Globulin (SHBG)
Time Frame: Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Serum concentrations of sex hormone binding globulin (SHBG)
Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Prostate Specific Antigen (PSA)
Time Frame: To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study
Serum concentrations of prostate specific antigen (PSA)
To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study
Follicle-stimulating Hormone (FSH)
Time Frame: Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Serum concentrations of follicle-stimulating hormone (FSH)
Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Maintenance of Testosterone Suppression at Week 52/ End of Study
Time Frame: Double-blind 28-Week Optional Extension Study from Week 24 to Week 52/End of Study
Proportion of patients failing to maintain castrate levels of T (T < 50 ng/dL). Testosterone suppression, defined as the absence of any T level measurement over 50 ng/dL during Weeks 24 to 52/End of Study
Double-blind 28-Week Optional Extension Study from Week 24 to Week 52/End of Study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
BHR Pharma, LLC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Q2 Solutions
H2O Clinical LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Roland Gerritsen van der Hoop, MD, PhD, BHR Pharma, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 14, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 10, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 23, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 27, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 28, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 31, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BHR-200-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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