PATCH: Prostate Adenocarcinoma TransCutaneous Hormones

Sponsor

University College, London (Other)

Overall Status

Recruiting

CT.gov ID

NCT00303784

Collaborator

Medical Research Council (Other)

2,200

Enrollment

Locations

Arms

185

Anticipated Duration (Months)

68.8

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2006

Anticipated Primary Completion Date :

Aug 1, 2021

Anticipated Study Completion Date :

Aug 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: FemSeven

Arm

Intervention/Treatment

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 Names:

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 Names:

FemSeven

Outcome Measures

Primary Outcome Measures

Progression-Free Survival [Up to 180 months]
Overall Survival [Up to 180 months]

Secondary Outcome Measures

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]
will be measured using patient-completed questionnaires, EORTC QLQ-C30 and PR25 which is prostate specific

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 120 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Locations

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