|- candidate number||2034|
|- NTR Number||NTR637|
|- ISRCTN||Incomplete info for ISRCTN|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||22-mrt-2006|
|- Secondary IDs||N/A |
|- Public Title||HIRISE (High-Risk women and hormonal Substitution Exposure).|
|- Scientific Title||Hormonal substitution after prophylactic adnectomy in women with an increased risk for breast-and ovarian cancer due to a genetic predisposition: HIRISE (High-Risk women and hormonal Substitution Exposure).|
|- hypothesis||The aim of the study is:|
1. To investigate the benefits and risks of hormonal substitution after prophylactic adnectomy in women with an increased risk for breast- and/or ovarian cancer due to a genetic predisposition;
2. To compare the effects and side-effects of conjugated estrogens, continuously combined with medroxyprogesterone acetate and tibolone.
|- Healt Condition(s) or Problem(s) studied||Breast cancer, Ovarian cancer|
|- Inclusion criteria||1. Prophylactic adnectomy not longer than five years ago, or scheduled to undergo prophylactic adnectomy within the next six months from randomization;|
2. Age 25-50 years;
3. Premenopausal at the time of prophylactic adnectomy;
4. Either proven BRCA 1 or BRCA 2 mutation carrier or member of an HBOC-family (50% risk carrier);
5. Have intact breast tissue (and do not consider prophylactic mastectomy in the next year);
6. Informed consent has been obtained.
|- Exclusion criteria||1. HST/ OAC (oral anticonceptive) intake in the last three months;|
2. History of breast cancer. Patients who have had adequately treated skin cancer (non-melanoma) or cervical carcinoma in situ are eligible. Furthermore, patients who have had another malignancy in the past, but have been disease free for more than 5 years are also eligible;
3. Abnormality on mammography that, according to the attending physician or radiologist, requires further diagnostic or therapeutic intervention;
4. Concomitant cardiovascular illness including: (recent) myocardial infarction, uncontrolled cardiac arrhytmias, angina pectoris, uncontrolled hypertension, and heart failure;
5. Current or history of deep venous thrombosis, thrombophlebitis, thromboembolic disease or suspicion of hereditary predisposition for developing venous thromboembolic disease or use of anticoagulation;
6. Abnormal endometrial thickness. For women having the ovaries still in situ, there is no maximum thickness. However, in women who were not exposed to endogenous or exogenous estrogens over the last three months, the double layer endometrial thickness should be less than 4 mm;
8. Abnormal Pap smear;
9. Known or suspected hypersensitivity to estrogen and/or progesterone and/or tibolone;
10. Concomitant disease for which the use of exogenous hormonal steroids is contraindicated;
11. Use of one or more of the following drugs within the last two months: hepatic microsomal enzyme-inducing anticonvulsant drugs or drugs known to affect or interfere with the pharmacokinetics of steroids (e.g. hydantoins and/or barbiturates, such as phenobarbital, Bellergal®, rifampicin, griseofulvin, primidone or carbamazepine);
12. Use of investigational drugs within the past 6 months;
13. Alcohol and/or drug abuse within the last 3 months or any other condition that might result in premature discontinuation, according to the opinion of the investigator;
14. Abnormal laboratory values considered being clinically relevant by the investigator.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||10-sep-2004|
|- planned closingdate||10-sep-2009|
|- Target number of participants||177|
|- Interventions||Patients will be randomized to receive either: |
1. 0.625 mg conjugated estrogens and 5 mg medroxyprogesterone acetate continuously combined (arm1) or
2. 2.5 mg tibolone continuously (arm 2).
Treatment will be preferentially administered for a period of at least two years. However, patients up to 50 years of age are eligible for the study as long as they intend to take the treatment medication for at least two years. In all patients, treatment may be continued until the age of 52 years, regardless the age at study entry.
Eligible women who are not willing to participate in the study because the absence of menopausal complaints and/or reluctance to take hormones will be asked to participate in a concomitant registration study.
In this group of women, the endpoints that will be measured and the data to collect are identical to the endpoints and data for the women participating in the intervention study.
|- Primary outcome||1. Change in mammographic breast density;|
2. Menopausal symptoms and sexuality.
|- Secondary outcome||1. Generic quality of life;|
3. Bone density;
4. Incidence of benign breast disorders;
5. Incidence of breast carcinoma (in situ and invasive);
6. Incidence of other malignancies;
7. Incidence of gynecological disorders;
8. Incidence of cardiovascular disease;
9. Incidence of biliary surgery;
10. Incidence of bone fractures;
11. LDL and HDL levels;
12. Androgen levels.
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD. Christien C.M. Buis|
|- CONTACT for SCIENTIFIC QUERIES||MD. PhD. Curt W. Burger|
|- Sponsor/Initiator |
(Source(s) of Monetary or Material Support)
|- Brief summary||N/A|
|- Main changes (audit trail)|
|- RECORD||22-mrt-2006 - 20-mei-2013|