Maintaining Suppression of Testosterone With Transdermal Estradiol Gel

Cancer of the Prostate Clinical Trial

— MASTERS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02349386
• Other study ID #: BHR-200-201
• Status: Terminated
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: January 10, 2018

Study information

• Verified date: April 2018
• Source: BHR Pharma, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: January 10, 2018
• Est. primary completion date: June 14, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer of the Prostate
• Prostatic Neoplasms

Intervention

Drug:
• BHR-200 (0.36% transdermal 17ß-estradiol gel)
An absorptive hydroalcoholic gel preparation containing 17ß-estradiol.
• Placebo
An absorptive hydroalcoholic gel preparation gel of the same ingredients as BHR-200, but without 17ß-estradiol.

Locations

Country	Name	City	State
United States	AccumetRX Clinical Trials	Albuquerque	New Mexico
United States	South Florida Medical Research	Aventura	Florida
United States	Urologic Consultants of Southeastern Pennsylvania (UCSEPA)	Bala-Cynwyd	Pennsylvania
United States	Adult Pediatric Urology, PC	Council Bluffs	Iowa
United States	Urology Clinics of North Texas	Dallas	Texas
United States	Advanced Urology Institute	Daytona Beach	Florida
United States	Eastern Urological Associates	Greenville	North Carolina
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Adult Pediatric Urology, PC	Omaha	Nebraska
United States	Associated Medical Professionals of NY (AMP of NY)	Syracuse	New York
United States	Urological Associates of Southern Arizona	Tucson	Arizona
United States	Delaware Valley Urology	Voorhees	New Jersey

Sponsors (3)

Lead Sponsor	Collaborator
BHR Pharma, LLC	H2O Clinical LLC, Q2 Solutions

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View Citation

Cox RL, Crawford ED. Estrogens in the treatment of prostate cancer. J Urol. 1995 Dec;154(6):1991-8. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Ockrim JL, Abel PD. Long term androgen deprivation therapy in prostate cancer. BMJ. 2008 Sep 22;337:a1361. doi: 10.1136/bmj.a1361. — View Citation

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. — View Citation

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. — View Citation

Sayed Y, Taxel P. The use of estrogen therapy in men. Curr Opin Pharmacol. 2003 Dec;3(6):650-4. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Luteinizing Hormone (LH)	Serum concentrations of luteinizing hormone (LH)	Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Other	Sex Hormone Binding Globulin (SHBG)	Serum concentrations of sex hormone binding globulin (SHBG)	Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Other	Prostate Specific Antigen (PSA)	Serum concentrations of prostate specific antigen (PSA)	To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study
Other	Follicle-stimulating Hormone (FSH)	Serum concentrations of follicle-stimulating hormone (FSH)	Reported for Baseline, Week 12, Week 24, Week 36 and Week 48
Other	Maintenance of Testosterone Suppression at 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
Primary	Maintenance of Testosterone Suppression at 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	Maintenance of Testosterone Suppression at 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
Secondary	Number of Patients Reporting Thromboembolic Adverse Events	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