Prostate Adenocarcinoma TransCutaneous Hormones
- Conditions
- Hot FlashesAnemiaOsteoporosisProstate CancerCardiovascular Complications
- Interventions
- Registration Number
- NCT00303784
- Lead Sponsor
- University College, London
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 2200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LHRH agonists Goserelin 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. Oestrogen Patches Estradiol 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).
- Primary Outcome Measures
Name Time Method Progression-Free Survival Up to 180 months Overall Survival Up to 180 months
- Secondary Outcome Measures
Name Time Method Other toxicity Up to 180 months Hormone activity by castrate levels of hormones Up to 180 months Cardiovascular morbidity Up to 180 months Cardiovascular mortality Up to 180 months Quality of Life Up to 24 months will be measured using patient-completed questionnaires, EORTC QLQ-C30 and PR25 which is prostate specific
Trial Locations
- Locations (32)
Walsgrave Hospital
🇬🇧Coventry, England, United Kingdom
Mayday University Hospital
🇬🇧Croydon, England, United Kingdom
Kidderminster Hospital
🇬🇧Kidderminster Worcestershire, England, United Kingdom
Ipswich Hospital
🇬🇧Ipswich, England, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, England, United Kingdom
Walsall Manor Hospital
🇬🇧Walsall, England, United Kingdom
Yeovil District Hospital
🇬🇧Yeovil, England, United Kingdom
Ayr Hospital
🇬🇧Ayr, Scotland, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Scotland, United Kingdom
Velindre Cancer Center at Velindre Hospital
🇬🇧Cardiff, Wales, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Hope Hospital
🇬🇧Salford, England, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom
Queen's Hospital
🇬🇧Burton-upon-Trent, England, United Kingdom
Hillingdon Hospital
🇬🇧Uxbridge, England, United Kingdom
James Cook University Hospital
🇬🇧Middlesbrough, England, United Kingdom
Grantham and District Hospital
🇬🇧Grantham, Lincolnshire, England, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, England, United Kingdom
Warwick Hospital
🇬🇧Warwick, England, United Kingdom
St. Mary's Hospital
🇬🇧London, England, United Kingdom
George Eliot Hospital
🇬🇧Nuneaton, England, United Kingdom
Mid Cheshire Hospitals Trust- Leighton Hopsital
🇬🇧Crewe, England, United Kingdom
Derbyshire Royal Infirmary
🇬🇧Derby, England, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, England, United Kingdom
Maidstone Hospital
🇬🇧Maidstone, England, United Kingdom
Kings Mill Hospital
🇬🇧Nottinghamshire, England, United Kingdom
Alexandra Healthcare NHS
🇬🇧Redditch, Worcestershire, England, United Kingdom
Scarborough General Hospital
🇬🇧Scarborough, England, United Kingdom
Stepping Hill Hospital
🇬🇧Stockport, England, United Kingdom
Worthing Hospital
🇬🇧Worthing, England, United Kingdom
Castle Hill Hospital
🇬🇧East Yorkshire, England, United Kingdom
Charing Cross Hospital
🇬🇧London, England, United Kingdom