Prostate Adenocarcinoma TransCutaneous Hormones

Prostate Cancer Clinical Trial

— PATCH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00303784
• Other study ID #: CDR0000455583
• Secondary ID: MRC-PATCHEU-2051
• Status: Recruiting
• Phase: Phase 3
• Start date: March 2006
• Est. completion date: August 2021

Study information

• Verified date: November 2020
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 2200
• Est. completion date: August 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Cardiovascular Complications
• Hot Flashes
• Osteoporosis
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Goserelin
3.6mg implant, in pre-filled syringe
• Estradiol
Each patch contains 3 mg of estradiol hemihydrate in a patch size of 30 cm2, releasing 100 micrograms of estradiol per 24 hours.

Locations

Country	Name	City	State
United Kingdom	Ayr Hospital	Ayr	Scotland
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Walsgrave Hospital	Coventry	England
United Kingdom	Mid Cheshire Hospitals Trust- Leighton Hopsital	Crewe	England
United Kingdom	Mayday University Hospital	Croydon	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Castle Hill Hospital	East Yorkshire	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Grantham and District Hospital	Grantham, Lincolnshire	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Kidderminster Hospital	Kidderminster Worcestershire	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	St. Mary's Hospital	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	Kings Mill Hospital	Nottinghamshire	England
United Kingdom	George Eliot Hospital	Nuneaton	England
United Kingdom	Alexandra Healthcare NHS	Redditch, Worcestershire	England
United Kingdom	Hope Hospital	Salford	England
United Kingdom	Scarborough General Hospital	Scarborough	England
United Kingdom	Stepping Hill Hospital	Stockport	England
United Kingdom	Hillingdon Hospital	Uxbridge	England
United Kingdom	Walsall Manor Hospital	Walsall	England
United Kingdom	Warwick Hospital	Warwick	England
United Kingdom	Worthing Hospital	Worthing	England
United Kingdom	Yeovil District Hospital	Yeovil	England

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival		Up to 180 months
Primary	Overall Survival		Up to 180 months
Secondary	Hormone activity by castrate levels of hormones		Up to 180 months
Secondary	Other toxicity		Up to 180 months
Secondary	Cardiovascular morbidity		Up to 180 months
Secondary	Cardiovascular mortality		Up to 180 months
Secondary	Quality of Life	will be measured using patient-completed questionnaires, EORTC QLQ-C30 and PR25 which is prostate specific	Up to 24 months

External Links

•   Study homepage at the MRC CTU at UCL