Evaluating the Effect of Candesartan vs Placebo in Prevention of Trastuzumab-associated Cardiotoxicity

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

Evaluating the effect of the angiotensin II-receptor (AT1) blocker candesartan vs placebo in prevention of trastuzumab-associated cardiotoxicity in patients with primary breast cancer treated with trastuzumab.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Netherlands Cancer Institute
• Collaborators: AstraZeneca; Roche Pharma AG
• Treatments: Angiotensin II; Angiotensinogen; Candesartan; Candesartan cilexetil; Trastuzumab

Criteria

Inclusion Criteria:

• Women aged ≥18 years

• WHO: ≤ 2

• 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).

• Serum creatinine <140 umol/l or creatinine clearance > 50 ml/min (by Cockcroft-Gault formula)

• Thyroid stimulating hormone between 0.5-3.9 MU/l

• Blood pressure systolic ≥ 140 mmHg and 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)

• LVEF ³ 50% assessed by multigated angiography (MUGA) or cardiac ultrasound

• Adjuvant regimen: trastuzumab start ≥ 3 weeks after day 1 of the last anthracycline chemotherapy cycle

• Trastuzumab treatment according to standard medical care

• Written informed consent to participate in the study

Exclusion Criteria:

• Prior anthracycline chemotherapy regimen or anti-HER2 therapy, or other prior biologic or immunotherapy for breast cancer treatment or any malignancy

• Previous malignancy requiring chemotherapy or radiotherapy

• Uncontrolled serious concurrent illness

• Patients with New York Heart Association (NYHA) class II/III/IV congestive heart failure

• Myocardial infarction < 6 months before randomization

• Treatment with ACE inhibitor, ATII blocker, or lithium. Patients treated with ACE inhibitor, or ATII blocker can switch (after randomization and during the chemotherapy period) to alternative antihypertensive therapy; see appendix 5.

• History of hypersensitivity to the study medication

• Pregnancy or breast feeding