Maintaining Suppression of Testosterone With Transdermal Estradiol Gel

NCT ID: NCT02349386

Last Updated: 2022-03-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2018-01-10

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.

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.

Conditions

Cancer of the Prostate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

An absorptive hydroalcoholic gel preparation containing 17β-estradiol.

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

An absorptive hydroalcoholic gel preparation containing 17β-estradiol.

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

An absorptive hydroalcoholic gel preparation containing 17β-estradiol.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

An absorptive hydroalcoholic gel preparation containing 17β-estradiol.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

BHR-200

Eligibility Criteria

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

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

Sponsors

H2O Clinical LLC

INDUSTRY

Sponsor Role: collaborator

Q2 Solutions

INDUSTRY

Sponsor Role: collaborator

BHR Pharma, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roland Gerritsen van der Hoop, MD, PhD

Role: STUDY_DIRECTOR

BHR Pharma, LLC

Locations

Urological Associates of Southern Arizona

Tucson, Arizona, United States

South Florida Medical Research

Aventura, Florida, United States

Advanced Urology Institute

Daytona Beach, Florida, United States

Adult Pediatric Urology, PC

Council Bluffs, Iowa, United States

Adult Pediatric Urology, PC

Omaha, Nebraska, United States

Delaware Valley Urology

Voorhees Township, New Jersey, United States

AccumetRX Clinical Trials

Albuquerque, New Mexico, United States

Associated Medical Professionals of NY (AMP of NY)

Syracuse, New York, United States

Eastern Urological Associates

Greenville, North Carolina, United States

Urologic Consultants of Southeastern Pennsylvania (UCSEPA)

Bala-Cynwyd, Pennsylvania, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Urology Clinics of North Texas

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 12686820 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16006886 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18809586 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17019433 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18422771 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23465742 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15641029 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 7500443 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17239273 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14644018 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BHR-200-201

Identifier Type: -

Identifier Source: org_study_id