Prostate Adenocarcinoma TransCutaneous Hormones

NCT00303784 | Unknown Phase 3

• 6 other identifiers: CDR0000455583MRC-PATCHEU-205106MRC-PR09ISRCTN704067182005-001030-33
• Study Type: interventional
• Target: 2,200
• Locations: 1 country
• Sites: 32

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.

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

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival

  Up to 180 months

• Overall Survival

  Up to 180 months

Secondary Outcomes (5)

• Hormone activity by castrate levels of hormones

  Up to 180 months

• Other toxicity

  Up to 180 months

• Cardiovascular morbidity

  Up to 180 months

• Cardiovascular mortality

  Up to 180 months

• Quality of Life

  Up to 24 months

Study Arms (2)

LHRH agonists

ACTIVE COMPARATOR

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

Oestrogen Patches

EXPERIMENTAL

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

Interventions

Goserelin DRUG

3.6mg implant, in pre-filled syringe

Also known as: Zoladex

LHRH agonists

Estradiol DRUG

Each patch contains 3 mg of estradiol hemihydrate in a patch size of 30 cm2, releasing 100 micrograms of estradiol per 24 hours.

Also known as: FemSeven

Oestrogen Patches

Eligibility Criteria

• Age: Up to 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University College, London: lead
• Medical Research Council: collaborator

Study Sites (32)

Queen's Hospital

Burton-on-Trent, England, DE13 0RB, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

RECRUITING

Walsgrave Hospital

Coventry, England, CV2 2DX, United Kingdom

RECRUITING

Mid Cheshire Hospitals Trust- Leighton Hopsital

Crewe, England, CW1 4QJ, United Kingdom

RECRUITING

Mayday University Hospital

Croydon, England, United Kingdom

RECRUITING

Derbyshire Royal Infirmary

Derby, England, DE1 2QY, United Kingdom

RECRUITING

Castle Hill Hospital

East Yorkshire, England, HU16 5JQ, United Kingdom

RECRUITING

Royal Devon and Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

RECRUITING

Grantham and District Hospital

Grantham, Lincolnshire, England, NG31 8DG, United Kingdom

RECRUITING

Ipswich Hospital

Ipswich, England, IP4 5PD, United Kingdom

RECRUITING

Kidderminster Hospital

Kidderminster Worcestershire, England, DY11 6RJ, United Kingdom

RECRUITING

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

RECRUITING

St. Mary's Hospital

London, England, W2 1NY, United Kingdom

RECRUITING

Charing Cross Hospital

London, England, W6 8RF, United Kingdom

RECRUITING

Maidstone Hospital

Maidstone, England, ME16 9QQ, United Kingdom

RECRUITING

James Cook University Hospital

Middlesbrough, England, TS4 3BW, United Kingdom

RECRUITING

Nottingham City Hospital

Nottingham, England, NG5 1PB, United Kingdom

RECRUITING

Kings Mill Hospital

Nottinghamshire, England, NG17 4JL, United Kingdom

RECRUITING

George Eliot Hospital

Nuneaton, England, CV10 7DJ, United Kingdom

RECRUITING

Alexandra Healthcare NHS

Redditch, Worcestershire, England, B98 7UB, United Kingdom

RECRUITING

Hope Hospital

Salford, England, M6 8HD, United Kingdom

RECRUITING

Scarborough General Hospital

Scarborough, England, YO12 6QL, United Kingdom

RECRUITING

Stepping Hill Hospital

Stockport, England, SK2 7JE, United Kingdom

RECRUITING

Hillingdon Hospital

Uxbridge, England, UB8 3NN, United Kingdom

RECRUITING

Walsall Manor Hospital

Walsall, England, WS2 9PS, United Kingdom

RECRUITING

Warwick Hospital

Warwick, England, CV34 5BW, United Kingdom

RECRUITING

Worthing Hospital

Worthing, England, BN11 2DH, United Kingdom

RECRUITING

Yeovil District Hospital

Yeovil, England, BA21 4AT, United Kingdom

RECRUITING

Ayr Hospital

Ayr, Scotland, KA6 6DX, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

RECRUITING

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

RECRUITING

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

RECRUITING

Related Publications (4)

• Gilbert DC, Nankivell M, Rush H, Clarke NW, Mangar S, Al-Hasso A, Rosen S, Kockelbergh R, Sundaram SK, Dixit S, Laniado M, McPhail N, Shaheen A, Brown S, Gale J, Deighan J, Marshall J, Duong T, Macnair A, Griffiths A, Amos CL, Sydes MR, James ND, Parmar MKB, Langley RE. A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design. Clin Oncol (R Coll Radiol). 2024 Jan;36(1):e11-e19. doi: 10.1016/j.clon.2023.10.054. Epub 2023 Nov 8.

  PMID: 37973477 DERIVED

• 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.

  PMID: 29388336 DERIVED

• 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.

  PMID: 26707868 DERIVED

• 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.

  PMID: 23465742 DERIVED

Related Links

• Study homepage at the MRC CTU at UCL

MeSH Terms

Conditions

Anemia; Hot Flashes; Osteoporosis; Prostatic Neoplasms

Interventions

Goserelin; Estradiol

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Paul D. Abel

  Charing Cross Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2006
• First Posted: March 17, 2006
• Study Start: March 1, 2006
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: November 27, 2020

Record last verified: 2020-11

Locations

GB (32)