Prospective, randomized, pharmacological intervention study; evaluating the effect of the angiotensin II-receptor (AT1) blocker candesartan versus placebo in prevention of trastuzumab-associated cardiotoxicity in patients with primary breast cancer treated with trastuzumab - M06HER

Conditions: WHO: 0-2 Serum creatinine <140 umol/l Thyroid stimulating hormone between 0.5-3.9 MU/l. Blood pressure systolic = 140 mmHg diastolic = 90 mmHg is acceptable at randomization. LVEF ? 50% assessed by multigated angiography (MUGA) or cardiac ultrasound

Registration Number: EUCTR2006-001707-11-NL

Lead Sponsor: KI-Av

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: Not specified

Inclusion Criteria

Women aged =18 years
2.WHO: 0-2
3.Strongly HER2-positive breast cancer, defined as an immunohistochemistry score of 3+ using the HercepTestTM or gene amplification by fluorescence in situ hybridization, or chromogenic in situ hybridization (CISH)
4.Serum creatinine <140 umol/l or creatinine clearance > 50 ml/min (by Cockcroft-Gault formula)
5.Thyroid stimulating hormone between 0.5-3.9 MU/l
6.Blood pressure systolic = 140 mmHg diastolic = 90 mmHg is acceptable at randomization. However prior to the first administration of trastuzumab blood pressure should be regulated and should be systolic = 100 mmHg and = 180 mmHg and diastolic = 60 mmHg and = 100 mmHg (blood pressure should be regulated according to the guidelines of appendix 5).
7.LVEF ? 50% assessed by multigated angiography (MUGA) or cardiac ultrasound.
8.(Neo-) adjuvant regimen: trastuzumab start = 3 weeks after day 1 of the last anthracycline chemotherapy cycle
9.Trastuzumab treatment according standard medical care
10.Written informed consent to participate in the study

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Prior anthracycline chemotherapy regimen or anti-HER2 therapy, or other prior biologic or immunotherapy for breast cancer treatment or any malignancy
2.Previous malignancy requiring chemotherapy or radiotherapy
3.Uncontrolled serious concurrent illness
4.Patients with New York Heart Association (NYHA) class III/IV congestive heart failure
5.Myocardial infarction < 6 months before randomization
6.Treatment with ACE inhibitors, ATII blockers, or lithium. Patients treated with ACE inhibitors or ATII blockers can switch (after randomization and during the chemotherapy period) to alternative antihypertensive therapy; see appendix 5.
7.History of hypersensitivity to the study medication
8.Pregnancy or breast feeding