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


Condition: Anemia, Cardiovascular Complications, Hot Flashes, Osteoporosis, Prostate Cancer

Intervention:

  • Drug: Goserelin
  • Drug: Estradiol

Purpose: 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 Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT00303784

Sponsor: Imperial College London

Primary Outcome Measures:

  • Measure: Progression-Free Survival
  • Time Frame: Up to 180 months
  • Safety Issue:
  • Measure: Overall Survival
  • Time Frame: Up to 180 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Hormone activity by castrate levels of hormones
  • Time Frame: Up to 180 months
  • Safety Issue:
  • Measure: Other toxicity
  • Time Frame: Up to 180 months
  • Safety Issue:
  • Measure: Cardiovascular morbidity
  • Time Frame: Up to 180 months
  • Safety Issue:
  • Measure: Cardiovascular mortality
  • Time Frame: Up to 180 months
  • Safety Issue:
  • Measure: Quality of Life
  • Time Frame: Up to 24 months
  • Safety Issue:

Estimated Enrollment: 2200

Study Start Date: March 2006

Phase: Phase 3

Eligibility:

  • Age: minimum N/A maximum 120 Years
  • Gender: Male

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

Locations:

  • Queen's Hospital
  • Burton-upon-Trent England DE13 0RB United Kingdom
  • Addenbrooke's Hospital
  • Cambridge England CB2 2QQ United Kingdom
  • Walsgrave Hospital
  • Coventry England CV2 2DX United Kingdom
  • Mid Cheshire Hospitals Trust- Leighton Hopsital
  • Crewe England CW1 4QJ United Kingdom
  • Mayday University Hospital
  • Croydon England United Kingdom
  • Derbyshire Royal Infirmary
  • Derby England DE1 2QY United Kingdom
  • Castle Hill Hospital
  • East Yorkshire England HU16 5JQ United Kingdom
  • Royal Devon and Exeter Hospital
  • Exeter England EX2 5DW United Kingdom
  • Grantham and District Hospital
  • Grantham, Lincolnshire England NG31 8DG United Kingdom
  • Ipswich Hospital
  • Ipswich England IP4 5PD United Kingdom
  • Kidderminster Hospital
  • Kidderminster Worcestershire England DY11 6RJ United Kingdom
  • Leeds Cancer Centre at St. James's University Hospital
  • Leeds England LS9 7TF United Kingdom
  • St. Mary's Hospital
  • London England W2 1NY United Kingdom
  • Charing Cross Hospital
  • London England W6 8RF United Kingdom
  • Maidstone Hospital
  • Maidstone England ME16 9QQ United Kingdom
  • James Cook University Hospital
  • Middlesbrough England TS4 3BW United Kingdom
  • Kings Mill Hospital
  • Nottinghamshire England NG17 4JL United Kingdom
  • Nottingham City Hospital
  • Nottingham England NG5 1PB United Kingdom
  • George Eliot Hospital
  • Nuneaton England CV10 7DJ United Kingdom
  • Alexandra Healthcare NHS
  • Redditch, Worcestershire England B98 7UB United Kingdom
  • Hope Hospital
  • Salford England M6 8HD United Kingdom
  • Scarborough General Hospital
  • Scarborough England YO12 6QL United Kingdom
  • Stepping Hill Hospital
  • Stockport England SK2 7JE United Kingdom
  • Hillingdon Hospital
  • Uxbridge England UB8 3NN United Kingdom
  • Walsall Manor Hospital
  • Walsall England WS2 9PS United Kingdom
  • Warwick Hospital
  • Warwick England CV34 5BW United Kingdom
  • Worthing Hospital
  • Worthing England BN11 2DH United Kingdom
  • Yeovil District Hospital
  • Yeovil England BA21 4AT United Kingdom
  • Ayr Hospital
  • Ayr Scotland KA6 6DX United Kingdom
  • Beatson West of Scotland Cancer Centre
  • Glasgow Scotland G12 0YN United Kingdom
  • Velindre Cancer Center at Velindre Hospital
  • Cardiff Wales CF14 2TL United Kingdom
  • University Hospital of Wales
  • Cardiff Wales CF14 4XW United Kingdom

View trial on ClinicalTrials.gov