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Prostate Adenocarcinoma TransCutaneous Hormones (PATCH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Imperial College London
Sponsor:
Collaborators:
Medical Research Council
University College, London
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT00303784
First received: March 15, 2006
Last updated: October 26, 2016
Last verified: October 2016
  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.


Condition Intervention Phase
Anemia
Cardiovascular Complications
Hot Flashes
Osteoporosis
Prostate Cancer
Drug: Goserelin
Drug: Estradiol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized-Controlled Trial of Transcutaneous Oestrogen Patches Versus LHRH Agonists in Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Progression-Free Survival [ Time Frame: Up to 180 months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Up to 180 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hormone activity by castrate levels of hormones [ Time Frame: Up to 180 months ] [ Designated as safety issue: No ]
  • Other toxicity [ Time Frame: Up to 180 months ] [ Designated as safety issue: Yes ]
  • Cardiovascular morbidity [ Time Frame: Up to 180 months ] [ Designated as safety issue: Yes ]
  • Cardiovascular mortality [ Time Frame: Up to 180 months ] [ Designated as safety issue: Yes ]
  • Quality of Life [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 2200
Study Start Date: March 2006
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: FemSeven

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

Ages Eligible for Study:   up to 120 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303784

Locations
United Kingdom
Queen's Hospital Recruiting
Burton-upon-Trent, England, United Kingdom, DE13 0RB
Contact: Contact Person    44-1283-566-333      
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Helen Patterson, MD    44-122324-5151 ext. 2523 and 2      
Walsgrave Hospital Recruiting
Coventry, England, United Kingdom, CV2 2DX
Contact: Contact Person    44-24-7660-2020      
Mid Cheshire Hospitals Trust- Leighton Hopsital Recruiting
Crewe, England, United Kingdom, CW1 4QJ
Contact: J. P. Logue, MD    44-1270-255-141      
Mayday University Hospital Recruiting
Croydon, England, United Kingdom
Contact: Robert A. Huddart, MD    44-20-8401-3000      
Derbyshire Royal Infirmary Recruiting
Derby, England, United Kingdom, DE1 2QY
Contact: Contact Person    44-1332-347-141 ext. 2407      
Castle Hill Hospital Recruiting
East Yorkshire, England, United Kingdom, HU16 5JQ
Contact: Contact Person    44-1482-875-875      
Royal Devon and Exeter Hospital Recruiting
Exeter, England, United Kingdom, EX2 5DW
Contact: Denise J. Sheehan, MD    44-1392-411-611      
Grantham and District Hospital Recruiting
Grantham, Lincolnshire, England, United Kingdom, NG31 8DG
Contact: P. Daruwala    44-1476-565-232      
Ipswich Hospital Recruiting
Ipswich, England, United Kingdom, IP4 5PD
Contact: Christopher Scrase, MD    44-147-370-4177      
Kidderminster Hospital Recruiting
Kidderminster Worcestershire, England, United Kingdom, DY11 6RJ
Contact: Contact Person    44-190-576-0635      
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Contact Person    44-113-206-6400      
St. Mary's Hospital Recruiting
London, England, United Kingdom, W2 1NY
Contact: Simon Stewart, MD    44-207-886-1132    s.stewart@imperial.ac.uk   
Charing Cross Hospital Recruiting
London, England, United Kingdom, W6 8RF
Contact: Paul D. Abel    44-20-8383-2268      
Maidstone Hospital Recruiting
Maidstone, England, United Kingdom, ME16 9QQ
Contact: Sharon Beesley    44-1622-729-000      
James Cook University Hospital Recruiting
Middlesbrough, England, United Kingdom, TS4 3BW
Contact: Contact Person    44-1642-850-850      
Kings Mill Hospital Recruiting
Nottinghamshire, England, United Kingdom, NG17 4JL
Contact: Contact Person    44-162-362-2515      
Nottingham City Hospital Recruiting
Nottingham, England, United Kingdom, NG5 1PB
Contact: Santhanam Sundar    44-115-969-1169    santhanam.sundar@nuh.nhs.uk   
George Eliot Hospital Recruiting
Nuneaton, England, United Kingdom, CV10 7DJ
Contact: Contact Person    44-024-7635-1351      
Alexandra Healthcare NHS Recruiting
Redditch, Worcestershire, England, United Kingdom, B98 7UB
Contact: Contact Person    44-015-2750-3030      
Hope Hospital Recruiting
Salford, England, United Kingdom, M6 8HD
Contact: Noel Clarke    44-161-206-5568      
Scarborough General Hospital Recruiting
Scarborough, England, United Kingdom, YO12 6QL
Contact: Andrew Robertson    44-1723-368-111      
Stepping Hill Hospital Recruiting
Stockport, England, United Kingdom, SK2 7JE
Contact: Contact Person    44-161-483-1010      
Hillingdon Hospital Recruiting
Uxbridge, England, United Kingdom, UB8 3NN
Contact: Alvan J. Pope    44-1895-238-282      
Walsall Manor Hospital Recruiting
Walsall, England, United Kingdom, WS2 9PS
Contact: Contact Person    44-1922-721-172      
Warwick Hospital Recruiting
Warwick, England, United Kingdom, CV34 5BW
Contact: Contact Person    44-1926 495-321      
Worthing Hospital Recruiting
Worthing, England, United Kingdom, BN11 2DH
Contact: Ralph Beard    44-1903-205-111 ext. 5559      
Yeovil District Hospital Recruiting
Yeovil, England, United Kingdom, BA21 4AT
Contact: Chris Parker    44-1935-475-122      
Ayr Hospital Recruiting
Ayr, Scotland, United Kingdom, KA6 6DX
Contact: Contact Person    44-1292-610-555      
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, Scotland, United Kingdom, G12 0YN
Contact: Contact Person    44-141-211-2123      
Velindre Cancer Center at Velindre Hospital Recruiting
Cardiff, Wales, United Kingdom, CF14 2TL
Contact: J. Lester, MD    44-29-2031-6292      
University Hospital of Wales Recruiting
Cardiff, Wales, United Kingdom, CF14 4XW
Contact: Howard Kynaston    44-2920-745-094      
Sponsors and Collaborators
Imperial College London
Medical Research Council
University College, London
Investigators
Study Chair: Paul D. Abel Charing Cross Hospital
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00303784     History of Changes
Other Study ID Numbers: CDR0000455583  MRC-PATCH  EU-205106  MRC-PR09  ISRCTN70406718  EUDRACT-2005-001030-33 
Study First Received: March 15, 2006
Last Updated: October 26, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
United Kingdom: National Institute for Health Research

Keywords provided by Imperial College London:
hot flashes
anemia
osteoporosis
cardiovascular complications
recurrent prostate cancer
stage III prostate cancer
stage IV prostate cancer
adenocarcinoma of the prostate

Additional relevant MeSH terms:
Hot Flashes
Prostatic Neoplasms
Adenocarcinoma
Osteoporosis
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Signs and Symptoms
Estradiol
Polyestradiol phosphate
Estrogens
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Goserelin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on December 02, 2016