Clinical trial NCT00303784: Prostate Adenocarcinoma TransCutaneous Hormones
Official title: A Randomized-Controlled Trial of Transcutaneous Oestrogen Patches Versus LHRH Agonists in Prostate Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Anemia
Cardiovascular Complications
Hot Flashes
Osteoporosis
Prostate Cancer
Keywords: hot flashes
anemia
osteoporosis
cardiovascular complications
recurrent prostate cancer
stage III prostate cancer
stage IV prostate cancer
adenocarcinoma of the prostate
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
First posted: 2006-03-17
Enrollment: 2200
Sex: MALE
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival
timeFrame: Up to 180 months
measure: Overall Survival
timeFrame: Up to 180 months
Secondary outcomes:
measure: Hormone activity by castrate levels of hormones
timeFrame: Up to 180 months
measure: Other toxicity
timeFrame: Up to 180 months
measure: Cardiovascular morbidity
timeFrame: Up to 180 months
measure: Cardiovascular mortality
timeFrame: Up to 180 months
measure: Quality of Life
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Crewe
country: United Kingdom
facility: Mid Cheshire Hospitals Trust- Leighton Hopsital
state: England
city: Croydon
country: United Kingdom
facility: Mayday University Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: East Yorkshire
country: United Kingdom
facility: Castle Hill Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Grantham, Lincolnshire
country: United Kingdom
facility: Grantham and District Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Kidderminster Worcestershire
country: United Kingdom
facility: Kidderminster Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: St. Mary's Hospital
state: England
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Nottinghamshire
country: United Kingdom
facility: Kings Mill Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
state: England
city: Redditch, Worcestershire
country: United Kingdom
facility: Alexandra Healthcare NHS
state: England
city: Salford
country: United Kingdom
facility: Hope Hospital
state: England
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
state: England
city: Stockport
country: United Kingdom
facility: Stepping Hill Hospital
state: England
city: Uxbridge
country: United Kingdom
facility: Hillingdon Hospital
state: England
city: Walsall
country: United Kingdom
facility: Walsall Manor Hospital
state: England
city: Warwick
country: United Kingdom
facility: Warwick Hospital
state: England
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: England
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Ayr
country: United Kingdom
facility: Ayr Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
Study officials:
affiliation: Charing Cross Hospital
name: Paul D. Abel
role: STUDY_CHAIR
References:
citation: Gilbert DC, Duong T, Sydes M, Bara A, Clarke N, Abel P, James N, Langley R, Parmar M; STAMPEDE and PATCH Trial Management Groups. Transdermal oestradiol as a method of androgen suppression for prostate cancer within the STAMPEDE trial platform. BJU Int. 2018 May;121(5):680-683. doi: 10.1111/bju.14153. Epub 2018 Feb 28. No abstract available.
citation: Langley RE, Kynaston HG, Alhasso AA, Duong T, Paez EM, Jovic G, Scrase CD, Robertson A, Cafferty F, Welland A, Carpenter R, Honeyfield L, Abel RL, Stone M, Parmar MK, Abel PD. A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol. Eur Urol. 2016 Jun;69(6):1016-25. doi: 10.1016/j.eururo.2015.11.030. Epub 2015 Dec 17.
citation: 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.