Prostate Adenocarcinoma TransCutaneous Hormones (PATCH)

November 24, 2020 updated by: University College, London

A Randomized-Controlled Trial of Transcutaneous Oestrogen Patches Versus LHRH Agonists in Prostate Cancer

RATIONALE: The increasingly prolonged and extended use of androgen deprivation therapy (ADT) in the treatment of prostate cancer, usually achieved through the administration of LHRH agonists, has raised concerns about long-term toxicities, in particular osteoporosis and adverse metabolic changes which may be associated with type II diabetes and increased cardiovascular risk. An alternative approach is to investigate other methods of ADT. Oral oestrogen has been shown to be as effective as LHRH and surgical orchidectomy in achieving castrate levels of testosterone and has equivalent or improved prostate cancer outcomes but is not used routinely as first-line therapy because of the risk of cardiovascular system (CVS) complications. The CVS complications have been attributed to first-pass hepatic metabolism. Administering oestrogen parenterally avoids the entero-hepatic circulation and so is expected to mitigate the risk of CVS toxicity whilst still effectively suppressing testosterone to castrate levels. This hypothesis has been supported by results from the early stages of this trial which have provided sufficient indication of the safety and efficacy of the patches to warrant further investigation of the treatment in this setting, as recommended by the IDMC..

PURPOSE: This randomized phase III trial is studying how well the estrogen skin patch works compared with luteinizing hormone-releasing hormone agonist injections in treating patients with locally advanced or metastatic prostate cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare the progression-free survival and overall survival of patients with locally advanced or metastatic prostate cancer treated with transcutaneous estrogen patches vs luteinizing hormone-releasing hormone analogues.

Secondary

  • Compare the cardiovascular system-related morbidity and mortality in patients treated with these regimens
  • Compare the activity of these treatments, in terms of castrate level of hormones, failure-free survival, and biochemical failure, in these patients.
  • Compare other toxicities, including osteoporosis, hot flushes, gynecomastia, and anemia, in patients treated with these regimens.
  • Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms at 1(control):1 (patch) ratio.

  • Arm I (control): Patients receive luteinizing hormone-releasing hormone agonists as per local practice in the absence of unacceptable toxicity.
  • Arm II (patch): Patients receive 4 transcutaneous estrogen patches, changing twice weekly for 4 weeks. Patients' testosterone levels are measured at week 4. Patients whose testosterone level is > 1.7 nmol/L continue to receive patch as before and have their testosterone level measured every 2 weeks. Patients whose testosterone level is < 1.7 nmol/L at week 4 or any other point receive 3 transcutaneous estrogen patches changed twice weekly in the absence of unacceptable toxicity.

Quality of life is assessed at baseline; at weeks 4, 8, and 12; every 3 months for 24 months.

After completion of study treatment, patients are followed periodically.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 2200 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

2200

Phase

  • Phase 3

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

  • United Kingdom
    • England
      • Burton-upon-Trent, England, United Kingdom, DE13 0RB
        • Recruiting
        • Queen's Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-1283-566-333
      • Cambridge, England, United Kingdom, CB2 2QQ
        • Recruiting
        • Addenbrooke's Hospital
        • Contact:
          • Helen Patterson, MD
          • Phone Number: 44-122324-5151 ext. 2523 and 2
      • Coventry, England, United Kingdom, CV2 2DX
        • Recruiting
        • Walsgrave Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-24-7660-2020
      • Crewe, England, United Kingdom, CW1 4QJ
        • Recruiting
        • Mid Cheshire Hospitals Trust- Leighton Hopsital
        • Contact:
          • J. P. Logue, MD
          • Phone Number: 44-1270-255-141
      • Croydon, England, United Kingdom
        • Recruiting
        • Mayday University Hospital
        • Contact:
          • Robert A. Huddart, MD
          • Phone Number: 44-20-8401-3000
      • Derby, England, United Kingdom, DE1 2QY
        • Recruiting
        • Derbyshire Royal Infirmary
        • Contact:
          • Contact Person
          • Phone Number: 44-1332-347-141 ext. 2407
      • East Yorkshire, England, United Kingdom, HU16 5JQ
        • Recruiting
        • Castle Hill Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-1482-875-875
      • Exeter, England, United Kingdom, Ex2 5DW
        • Recruiting
        • Royal Devon and Exeter Hospital
        • Contact:
          • Denise J. Sheehan, MD
          • Phone Number: 44-1392-411-611
      • Grantham, Lincolnshire, England, United Kingdom, NG31 8DG
        • Recruiting
        • Grantham and District Hospital
        • Contact:
          • P. Daruwala
          • Phone Number: 44-1476-565-232
      • Ipswich, England, United Kingdom, IP4 5PD
        • Recruiting
        • Ipswich Hospital
        • Contact:
          • Christopher Scrase, MD
          • Phone Number: 44-147-370-4177
      • Kidderminster Worcestershire, England, United Kingdom, DY11 6RJ
        • Recruiting
        • Kidderminster Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-190-576-0635
      • Leeds, England, United Kingdom, LS9 7TF
        • Recruiting
        • Leeds Cancer Centre at St. James's University Hospital
      • London, England, United Kingdom, W2 1NY
        • Recruiting
        • St. Mary's Hospital
        • Contact:
      • London, England, United Kingdom, W6 8RF
        • Recruiting
        • Charing Cross Hospital
        • Contact:
          • Paul D. Abel
          • Phone Number: 44-20-8383-2268
      • Maidstone, England, United Kingdom, ME16 9QQ
        • Recruiting
        • Maidstone Hospital
        • Contact:
          • Sharon Beesley
          • Phone Number: 44-1622-729-000
      • Middlesbrough, England, United Kingdom, TS4 3BW
        • Recruiting
        • James Cook University Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-1642-850-850
      • Nottingham, England, United Kingdom, NG5 1PB
      • Nottinghamshire, England, United Kingdom, NG17 4JL
        • Recruiting
        • Kings Mill Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-162-362-2515
      • Nuneaton, England, United Kingdom, CV10 7DJ
        • Recruiting
        • George Eliot Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-024-7635-1351
      • Redditch, Worcestershire, England, United Kingdom, B98 7UB
        • Recruiting
        • Alexandra Healthcare NHS
        • Contact:
          • Contact Person
          • Phone Number: 44-015-2750-3030
      • Salford, England, United Kingdom, M6 8HD
        • Recruiting
        • Hope Hospital
        • Contact:
          • Noel Clarke
          • Phone Number: 44-161-206-5568
      • Scarborough, England, United Kingdom, YO12 6QL
        • Recruiting
        • Scarborough General Hospital
        • Contact:
          • Andrew Robertson
          • Phone Number: 44-1723-368-111
      • Stockport, England, United Kingdom, SK2 7JE
        • Recruiting
        • Stepping Hill Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-161-483-1010
      • Uxbridge, England, United Kingdom, UB8 3NN
        • Recruiting
        • Hillingdon Hospital
        • Contact:
          • Alvan J. Pope
          • Phone Number: 44-1895-238-282
      • Walsall, England, United Kingdom, WS2 9PS
        • Recruiting
        • Walsall Manor Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-1922-721-172
      • Warwick, England, United Kingdom, CV34 5BW
        • Recruiting
        • Warwick Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-1926 495-321
      • Worthing, England, United Kingdom, BN11 2DH
        • Recruiting
        • Worthing Hospital
        • Contact:
          • Ralph Beard
          • Phone Number: 44-1903-205-111 ext. 5559
      • Yeovil, England, United Kingdom, BA21 4AT
        • Recruiting
        • Yeovil District Hospital
        • Contact:
          • Chris Parker
          • Phone Number: 44-1935-475-122
    • Scotland
      • Ayr, Scotland, United Kingdom, KA6 6DX
        • Recruiting
        • Ayr Hospital
        • Contact:
          • Contact Person
          • Phone Number: 44-1292-610-555
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Recruiting
        • Beatson West of Scotland Cancer Centre
        • Contact:
          • Contact Person
          • Phone Number: 44-141-211-2123
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 2TL
        • Recruiting
        • Velindre Cancer Center at Velindre Hospital
        • Contact:
          • J. Lester, MD
          • Phone Number: 44-29-2031-6292
      • Cardiff, Wales, United Kingdom, CF14 4XW
        • Recruiting
        • University Hospital of Wales
        • Contact:
          • Howard Kynaston
          • Phone Number: 44-2920-745-094

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

No older than 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

DISEASE CHARACTERISTICS:

  • Must meet 1 of the following criteria:

    • Newly diagnosed patients with any of the following:

      • Stage T3 or T4, NX, M0 histologically confirmed prostate adenocarcinoma with prostate-specific antigen (PSA) ≥ 20 ng/mL or Gleason score ≥ 6
      • Any T, N+, M0, or any T, any N, M+ histologically confirmed prostate adenocarcinoma
      • Multiple sclerotic bone metastases with a PSA ≥ 50 ng/mL without histological confirmation

    • Patients with histologically confirmed prostate adenocarcinoma previously treated with radical surgery or radiotherapy who are currently in relapse with on of the following:

      • PSA ≥ 4 ng/mL and rising with doubling time less than 6 months
      • PSA ≥ 20 ng/mL
  • Must have written informed consent
  • Intention to treat with long-term androgen-deprivation therapy
  • Normal testosterone level prior to hormonal treatment

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • No other prior or current malignant disease or cardiovascular system disease that is likely to interfere with study treatment or assessment

  • No cardiovascular disease, including any of the following:

    • History of cerebral ischemia (e.g., stroke or transient ischemic attack) within the past 2 years
    • History of deep vein thrombosis or pulmonary embolism confirmed radiologically

    • History of myocardial infarction (MI) within the past 6 months OR MI more than 6 months ago with evidence of q-wave anterior infarct on ECG

      • ECHO or MUGA required for patients with history of ischemic heart disease
    • Left Ventricular Ejection Fraction ≤ 40%
  • No condition or situation that could preclude protocol treatment or compliance with follow-up schedule

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 12 months since prior adjuvant or neoadjuvant hormonal therapy for localized prostate cancer AND therapy lasted ≤ 12 months in duration
  • No prior systemic therapy for locally advanced or metastatic prostate cancer
  • No concurrent participation in another clinical trial of prostate cancer treatment that would preclude study therapy or outcome measures
  • Concurrent prophylactic radiotherapy to prevent gynecomastia allowed

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: LHRH agonists
Patients randomised to the control arm will receive continuous treatment with LHRH agonists as per local practice. Treatment should continue for at least 3 years. LHRH antagonists, such as degarelix, are not allowed on the trial. The recommended "anti-flare" medication is bicalutamide and should be prescribed according to local practice. Control arm medication should be obtained from the hospital pharmacy or GP as per local practice.
Drug: Goserelin
3.6mg implant, in pre-filled syringe
Other Names:
  • Zoladex
Experimental: Oestrogen Patches
Patients randomised to the investigational arm will receive transcutaneous oestrogen patches (100 micrograms/24 hours). Treatment should be planned to continue for at least 3 years. For patients prescribed bicalutamide or flutamide prior to randomisation, this treatment should be discontinued before treatment with the patches can commence (no washout period is needed).
Drug: Estradiol
Each patch contains 3 mg of estradiol hemihydrate in a patch size of 30 cm2, releasing 100 micrograms of estradiol per 24 hours.
Other Names:
  • FemSeven

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-Free Survival
Time Frame: Up to 180 months
Up to 180 months
Overall Survival
Time Frame: Up to 180 months
Up to 180 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hormone activity by castrate levels of hormones
Time Frame: Up to 180 months
Up to 180 months
Other toxicity
Time Frame: Up to 180 months
Up to 180 months
Cardiovascular morbidity
Time Frame: Up to 180 months
Up to 180 months
Cardiovascular mortality
Time Frame: Up to 180 months
Up to 180 months
Quality of Life
Time Frame: Up to 24 months
will be measured using patient-completed questionnaires, EORTC QLQ-C30 and PR25 which is prostate specific
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

Medical Research Council

Investigators

  • Study Chair: Paul D. Abel, Charing Cross Hospital

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

Helpful Links

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)

March 1, 2006

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

August 1, 2021

Study Registration Dates

First Submitted

March 15, 2006

First Submitted That Met QC Criteria

March 15, 2006

First Posted (Estimate)

March 17, 2006

Study Record Updates

Last Update Posted (Actual)

November 27, 2020

Last Update Submitted That Met QC Criteria

November 24, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000455583
  • MRC-PATCH (Other Grant/Funding Number: MRC)
  • EU-205106 (Other Identifier: EU)
  • MRC-PR09 (Other Identifier: MRC)
  • ISRCTN70406718 (Registry Identifier: ISRCTN70406718)
  • 2005-001030-33 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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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