- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02349386
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
Terminated
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
34
Phase
- 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
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Arizona
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Tucson, Arizona, United States, 85741
- Urological Associates of Southern Arizona
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Florida
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Aventura, Florida, United States, 33180
- South Florida Medical Research
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Daytona Beach, Florida, United States, 32114
- Advanced Urology Institute
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Iowa
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Council Bluffs, Iowa, United States, 51501
- Adult Pediatric Urology, PC
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Nebraska
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Omaha, Nebraska, United States, 68114
- Adult Pediatric Urology, PC
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New Jersey
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Voorhees, New Jersey, United States, 08043
- Delaware Valley Urology
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New Mexico
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Albuquerque, New Mexico, United States, 87109
- AccumetRX Clinical Trials
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New York
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Syracuse, New York, United States, 13210
- Associated Medical Professionals of NY (AMP of NY)
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North Carolina
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Greenville, North Carolina, United States, 27834
- Eastern Urological Associates
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Pennsylvania
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Bala-Cynwyd, Pennsylvania, United States, 19044
- Urologic Consultants of Southeastern Pennsylvania (UCSEPA)
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South Carolina
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Myrtle Beach, South Carolina, United States, 29572
- Carolina Urologic Research Center
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Texas
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Dallas, Texas, United States, 75231
- Urology Clinics of North Texas
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-
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
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Males, Ages 18 and older
- Body Mass Index (BMI) between 18 and 35 kg/m2 (inclusive)
- Not currently hospitalized
- Clinical indication of adenocarcinoma of the prostate evidenced by a biopsy report on record
- 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.
- Able to initiate Screening procedures 2 weeks prior to the next scheduled injection with a GnRH agonist
- Willing to discontinue current ADT regimen for the duration of the study
- T level less than 50 ng/dL at Screening
- WHO/ECOG performance status of 0 or 1
- Life expectancy of at least 1 year
- Adequate renal function demonstrated by having normal blood urea nitrogen (BUN) and Creatinine Screening lab values
Exclusion Criteria:
- History or presence of allergic or adverse response to estradiol
- Presence of symptomatic metastatic disease, risk of spinal cord compression or urinary obstruction
- 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)
- History within the past 2 years of myocardial infarction or a coronary vascular procedure (e.g. percutaneous coronary intervention, coronary artery bypass graft)
- History of congestive heart failure
- Use of any investigational drug, biologic, or device within 28 days prior to the first dose of study gel
- 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
- Hematological parameters (Hematocrit or Hemoglobin) outside 20% of the upper or lower limits of normal at Screening
- Active skin rash, sunburn, or other skin disorder on the upper arm(s) that requires treatment or may affect skin absorption of study gel
- Resting uncontrolled hypertension (HTN) (160/100 mmHg) at Screening
- 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
- 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 |
Intervention / Treatment |
---|---|
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.
|
An absorptive hydroalcoholic gel preparation containing 17β-estradiol.
Other Names:
|
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.
|
An absorptive hydroalcoholic gel preparation containing 17β-estradiol.
Other Names:
|
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.
|
An absorptive hydroalcoholic gel preparation containing 17β-estradiol.
Other Names:
|
Placebo Comparator: Placebo
1, 2 or 3 mL of Placebo gel containing 0 mg estradiol applied daily for up to 52 weeks.
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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
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
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
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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
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Luteinizing Hormone (LH)
Time Frame: Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
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Serum concentrations of luteinizing hormone (LH)
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Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
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Sex Hormone Binding Globulin (SHBG)
Time Frame: Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
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Serum concentrations of sex hormone binding globulin (SHBG)
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Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
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Prostate Specific Antigen (PSA)
Time Frame: To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study
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Serum concentrations of prostate specific antigen (PSA)
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To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study
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Follicle-stimulating Hormone (FSH)
Time Frame: Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
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Serum concentrations of follicle-stimulating hormone (FSH)
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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
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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
Investigators
- 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
- Ockrim JL, Lalani EN, Laniado ME, Carter SS, Abel PD. Transdermal estradiol therapy for advanced prostate cancer--forward to the past? J Urol. 2003 May;169(5):1735-7. doi: 10.1097/01.ju.0000061024.75334.40.
- Ockrim JL, Lalani el-N, Kakkar AK, Abel PD. Transdermal estradiol therapy for prostate cancer reduces thrombophilic activation and protects against thromboembolism. J Urol. 2005 Aug;174(2):527-33; discussion 532-3. doi: 10.1097/01.ju.0000165567.99142.1f.
- Ockrim JL, Abel PD. Long term androgen deprivation therapy in prostate cancer. BMJ. 2008 Sep 22;337:a1361. doi: 10.1136/bmj.a1361. No abstract available.
- Ockrim J, Lalani el-N, Abel P. Therapy Insight: parenteral estrogen treatment for prostate cancer--a new dawn for an old therapy. Nat Clin Pract Oncol. 2006 Oct;3(10):552-63. doi: 10.1038/ncponc0602.
- Langley RE, Godsland IF, Kynaston H, Clarke NW, Rosen SD, Morgan RC, Pollock P, Kockelbergh R, Lalani el-N, Dearnaley D, Parmar M, Abel PD. Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first-line hormonal therapy in patients with locally advanced or metastatic prostate cancer. BJU Int. 2008 Aug;102(4):442-5. doi: 10.1111/j.1464-410X.2008.07583.x. Epub 2008 Apr 16.
- Langley RE, Cafferty FH, Alhasso AA, Rosen SD, Sundaram SK, Freeman SC, Pollock P, Jinks RC, Godsland IF, Kockelbergh R, Clarke NW, Kynaston HG, Parmar MK, Abel PD. Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing-hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09). Lancet Oncol. 2013 Apr;14(4):306-16. doi: 10.1016/S1470-2045(13)70025-1. Epub 2013 Mar 4.
- Bland LB, Garzotto M, DeLoughery TG, Ryan CW, Schuff KG, Wersinger EM, Lemmon D, Beer TM. Phase II study of transdermal estradiol in androgen-independent prostate carcinoma. Cancer. 2005 Feb 15;103(4):717-23. doi: 10.1002/cncr.20857.
- Cox RL, Crawford ED. Estrogens in the treatment of prostate cancer. J Urol. 1995 Dec;154(6):1991-8.
- Lycette JL, Bland LB, Garzotto M, Beer TM. Parenteral estrogens for prostate cancer: can a new route of administration overcome old toxicities? Clin Genitourin Cancer. 2006 Dec;5(3):198-205. doi: 10.3816/CGC.2006.n.037.
- Sayed Y, Taxel P. The use of estrogen therapy in men. Curr Opin Pharmacol. 2003 Dec;3(6):650-4. doi: 10.1016/j.coph.2003.07.004.
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)
July 1, 2015
Primary Completion (Actual)
June 14, 2017
Study Completion (Actual)
January 10, 2018
Study Registration Dates
First Submitted
January 23, 2015
First Submitted That Met QC Criteria
January 27, 2015
First Posted (Estimate)
January 28, 2015
Study Record Updates
Last Update Posted (Actual)
March 31, 2022
Last Update Submitted That Met QC Criteria
March 8, 2022
Last Verified
April 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Estrogens
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptive Agents, Female
- Estradiol
- Estradiol 17 beta-cypionate
- Estradiol 3-benzoate
- Polyestradiol phosphate
Other Study ID 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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