Maintaining Suppression of Testosterone With Transdermal Estradiol Gel

NCT02349386 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: BHR-200-201
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Cancer of the Prostate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Maintenance of Testosterone Suppression at Week 24

  Week 24

• Number of Patients Reporting Thromboembolic Adverse Events

  To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study

Other Outcomes (5)

• Luteinizing Hormone (LH)

  Reported for Baseline, Week 12, Week 24, Week 36 and Week 48

• Sex Hormone Binding Globulin (SHBG)

  Reported for Baseline, Week 12, Week 24, Week 36 and Week 48

• Prostate Specific Antigen (PSA)

  To Week 52/End of Study: Both 24-Week Main Study and Optional 28-Week Extension Study

Study Arms (4)

BHR-200 Low Dose

EXPERIMENTAL

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)

BHR-200 Mid Dose

EXPERIMENTAL

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)

BHR-200 High Dose

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

1, 2 or 3 mL of Placebo gel containing 0 mg estradiol applied daily for up to 52 weeks.

Drug: Placebo

Interventions

BHR-200 (0.36% transdermal 17β-estradiol gel) DRUG

An absorptive hydroalcoholic gel preparation containing 17β-estradiol.

Also known as: BHR-200

BHR-200 High Dose; BHR-200 Low Dose; BHR-200 Mid Dose

Placebo DRUG

An absorptive hydroalcoholic gel preparation gel of the same ingredients as BHR-200, but without 17β-estradiol.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BHR Pharma, LLC: lead
• H2O Clinical LLC: collaborator
• Q2 Solutions: collaborator

Study Sites (12)

Urological Associates of Southern Arizona

Tucson, Arizona, 85741, United States

Location

South Florida Medical Research

Aventura, Florida, 33180, United States

Location

Advanced Urology Institute

Daytona Beach, Florida, 32114, United States

Location

Adult Pediatric Urology, PC

Council Bluffs, Iowa, 51501, United States

Location

Adult Pediatric Urology, PC

Omaha, Nebraska, 68114, United States

Location

Delaware Valley Urology

Voorhees Township, New Jersey, 08043, United States

Location

AccumetRX Clinical Trials

Albuquerque, New Mexico, 87109, United States

Location

Associated Medical Professionals of NY (AMP of NY)

Syracuse, New York, 13210, United States

Location

Eastern Urological Associates

Greenville, North Carolina, 27834, United States

Location

Urologic Consultants of Southeastern Pennsylvania (UCSEPA)

Bala-Cynwyd, Pennsylvania, 19044, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Urology Clinics of North Texas

Dallas, Texas, 75231, United States

Location

Related Publications (10)

• 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.

  PMID: 12686820 BACKGROUND

• 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.

  PMID: 16006886 BACKGROUND

• 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.

  PMID: 18809586 BACKGROUND

• 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.

  PMID: 17019433 BACKGROUND

• 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.

  PMID: 18422771 BACKGROUND

• 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.

  PMID: 23465742 BACKGROUND

• 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.

  PMID: 15641029 BACKGROUND

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

  PMID: 7500443 BACKGROUND

• 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.

  PMID: 17239273 BACKGROUND

• 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.

  PMID: 14644018 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Global Chief Medical Officer
• Organization: Besins Healthcare Ireland Ltd

clinicaldevelopment@besins-healthcare.com

+353 87 1039215

Study Officials

• Roland Gerritsen van der Hoop, MD, PhD

  BHR Pharma, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: January 28, 2015
• Study Start: July 1, 2015
• Primary Completion: June 14, 2017
• Study Completion: January 10, 2018
• Last Updated: March 31, 2022
• Results First Posted: March 31, 2022

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)