To analyse the safety of oestradiol in the setting of endocrine treatment for locally extended prostate cancer adjuvant to radiotherapy.
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incidence of cardiovascular events (number of cardiovascular events per 100
patient years).
Secondary outcome
- Compliance to the study intervention (measured by oestradiol serum levels at
every visit).
- Incidence of endocrine related side effects.
- Changes of metabolic serum parameters (liver function (SGOT, SGPT,
bilirubin), endocrine (oestradiol, testosterone, PSA), lipid profile (HbA1c,
cholesterol, HDL).
- Time to reach testosterone castration levels (during run-in period, T * 1.7
nmol/L).
- Quality of Life (EORTC QC 30, PR25 potency, overall).
Background summary
Endocrine treatment is the mainstay for metastatic prostate cancer. During the
last three decades, medical castration has been chosen above surgical
castration by orchidectomy. Current options involve predominantly the use of
relatively expensive Luteinizing-hormone-releasing hormone (LHRH) agonists
because of their reported preference with regard to the incidence of
thromboembolic events when compared to oestrogens. [1] However, LHRH agonists
(LHRHa) are associated with long-term toxic effects, including osteoporosis,
and adverse metabolic changes. The use of parenteral oestrogen is under trial
in the PATCH-trial that reported recently on the intermediate long term effects
of transdermal oestradiol application in men who require permanent androgen
deprivation. The thromboembolic complications associated with transdermal
oestrogen appear similar to that of LHRH agonists in this randomised study. [1]
As parenteral oestrogen administration avoids the entero-hepatic circulation
(first pass hepatic metabolism) it is associated with a reduced incidence of
cardiovascular toxicity compared with oral oestrogen. [2] The recently updated
prostate cancer guideline of the Dutch Urological Society, stated that though
parenteral oestrogen treatment could be safe in patients without cardiovascular
risk factors, further study is needed before this therapy might become standard
care. [3] However, oestrogen treatment is already regularly prescribed by a lot
of Dutch urologists (amongst which the urologists participating in the current
trial) for androgen deprivation in patients with prostate cancer, also in the
earlier phase of the disease. Treatment with oestrogens is reimbursed by the
health care insurances.
During this study it will be analysed whether transdermal applied oestrogens in
the earlier phase of the disease, that is during the adjuvant endocrine setting
during curative treatment for locally extended prostate cancer, might even be
less toxic compared to the standard medical castration therapy.
1. Langley, R.E., et al., 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. 14(4): p.
306-16.
2. Turgeon, J.L., et al., Hormone therapy: physiological complexity belies
therapeutic simplicity. Science, 2004. 304(5675): p. 1269-73.
3. Reijke, T.M.d., Richtlijn Prostaatcarcinoom, 2013: Oncoline.
Study objective
To analyse the safety of oestradiol in the setting of endocrine treatment for
locally extended prostate cancer adjuvant to radiotherapy.
Study design
This pilot study is a multicentre, open label, non-randomized, intervention
study.
Intervention
During a run*in period of approximately 3 months subjects will self-administer
four skin patches for transdermal application of oestradiol (100 *g per 24 h)
per time, which will be changed twice weekly. After the run-in period, a
regimen of three oestrogen patches changed twice weekly will be given as soon
as castrate testosterone concentrations (1.7 nmol/L or lower) have been
reached. Subjects will be treated with oestradiol patches for a period of two
years.
Study burden and risks
The burden related to participation in this study are the two extra visits at
week 0 and 4 (run in period), filling in questionnaires at 7 visits, and the
extra blood/serum withdrawal for analysis of hormones and related metabolites
and/or safety measurements (8.5 * 25 ml per withdrawal, 8 times). Weight and
blood pressure (BP) are measured 7 times, otherwise no physical exams or tests
will be done. Therefore the risks for this study with regard to extra tests are
negligible.
Side effects expected based on information of the PATCH trial are:
- Cardiovascular (thromboembolism): 5%
- Gynaecomastia: 75% (several grades of severity)
- Hot flushes: 25%
- Dermatological problems: 42%
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
1) Men * 18 years.
2) Locally advanced prostate cancer.
3) Selected for at least two years of adjuvant endocrine therapy and EBRT.
4) Signed informed consent.
5) Testosterone serum level > 6 nmol/l.
Exclusion criteria
1) Current endocrine treatment or previous therapy within 6 months (5-alpha
reductase inhibitors are permitted).
2) Previous radiological confirmed deep venous thrombosis or pulmonary embolus.
3) Cerebrovascular event (TIA or CVA) within 6 months.
4) Coronary heart disease within 6 months.
5) Instable angina pectoris within 6 months.
6) Congenital thrombofilic diseases.
7) Thrombolic disease within 6 months.
8) Heart failure as defined by NYHA class >2.
9) Hypertension (not corrected by medication) >160/100 mmHg. If either systolic
or diastolic value is higher than these values the patient is not eligible.
10) Suboptimal regulated diabetes mellitus or de novo diabetes mellitus as
defined by HbA1c of over 6,5% (48 mmol/mol).
11) Rheumatoid arthritis.
12) Impaired renal function as defined by a GFR < 30 ml/ min/1,73 m2
13) Acute liver failure or reduced liver function showing as increased serum
parameters (SGOT, SGPT, bilirubine > 2.5 times normal).
14) Porfyria.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-005479-42-NL |
| CCMO | NL47698.078.14 |
| OMON | NL-OMON20250 |