AzTrials
AzTrials

Cancer of the ProstatePhase 2MASTERSNCT02349386

Maintaining Suppression of Testosterone With Transdermal Estradiol Gel

A Phase 2 study testing BHR-200 (0.36% transdermal 17β-estradiol gel) in people with Cancer of the Prostate, run by BHR Pharma, LLC at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Cancer of the Prostate
What is being tested?
BHR-200 (0.36% transdermal 17β-estradiol gel)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
34 participants
Where
12 sitesUnited States
Study dates
Jul 2015to 10 Jan 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites
  • AccumetRX Clinical Trials

    Albuquerque, New Mexico, 87109

  • South Florida Medical Research

    Aventura, Florida, 33180

  • Urologic Consultants of Southeastern Pennsylvania (UCSEPA)

    Bala-Cynwyd, Pennsylvania, 19044

  • Adult Pediatric Urology, PC

    Council Bluffs, Iowa, 51501

  • Urology Clinics of North Texas

    Dallas, Texas, 75231

  • Advanced Urology Institute

    Daytona Beach, Florida, 32114

  • Eastern Urological Associates

    Greenville, North Carolina, 27834

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • Adult Pediatric Urology, PC

    Omaha, Nebraska, 68114

  • Associated Medical Professionals of NY (AMP of NY)

    Syracuse, New York, 13210

  • Urological Associates of Southern Arizona

    Tucson, Arizona, 85741

  • Delaware Valley Urology

    Voorhees Township, New Jersey, 08043

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
BHR-200 (0.36% transdermal 17β-estradiol gel), Placebo
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called BHR-200

    An absorptive hydroalcoholic gel preparation containing 17β-estradiol.

  • PlaceboDrug

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

Study groups in NCT02349386
Study groupRoleWhat they receive
BHR-200 Low DoseExperimental3 mg estradiol per 1 mL 0.36% BHR-200 (transdermal 17β-estradiol gel) applied daily to the skin for up to 52 weeks.
Receives: Drug: BHR-200 (0.36% transdermal 17β-estradiol gel)
BHR-200 Mid DoseExperimental6 mg estradiol per 2 mL 0.36% BHR-200 (transdermal 17β-estradiol gel) applied daily to the skin for up to 52 weeks.
Receives: Drug: BHR-200 (0.36% transdermal 17β-estradiol gel)
BHR-200 High DoseExperimental9 mg estradiol per 3 mL 0.36% BHR-200 (transdermal 17β-estradiol gel) applied daily to the skin for up to 52 weeks.
Receives: Drug: BHR-200 (0.36% transdermal 17β-estradiol gel)
PlaceboPlacebo comparator1, 2 or 3 mL of Placebo gel containing 0 mg estradiol applied daily for up to 52 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 12

Secondary outcomes (2)
  1. 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.

    Measured: Week 24

  2. Number of Patients Reporting Thromboembolic Adverse Events

    Number of patients and severity of thromboembolic adverse events

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2015 (estimated)
  2. Study startJul 2015
  3. Primary completion14 Jun 2017
  4. Study completion10 Jan 2018

Why it stopped: Inability to recruit patients

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02349386
Sponsor's protocol ID
BHR-200-201
Acronym
MASTERS
Status last verified
Apr 2018
First submitted
23 Jan 2015
Last updated
31 Mar 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 12686820
  • 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.

    PubMed 16006886
  • 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.

    PubMed 18809586
  • 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.

    PubMed 17019433
  • 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.

    PubMed 18422771
  • 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.

    PubMed 23465742
  • 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.

    PubMed 15641029
  • Cox RL, Crawford ED. Estrogens in the treatment of prostate cancer. J Urol. 1995 Dec;154(6):1991-8.

    PubMed 7500443
  • 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.

    PubMed 17239273
  • 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.

    PubMed 14644018

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BHR-200 (0.36% transdermal 17β-estradiol gel) in people with Cancer of the Prostate, run by BHR Pharma, LLC at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maintenance of Testosterone Suppression at Week 12 (time frame: Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02349386, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in