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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00459771
Recruitment Status : Completed
First Posted : April 12, 2007
Last Update Posted : December 2, 2014
Roche Pharma AG
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: AT1 blocker candesartan Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective, Randomized, Pharmacological Intervention Study; Evaluating Effect of the Angiotensin II-receptor (AT1) Blocker Candesartan vs Placebo in Prevention of Trastuzumab-associated Cardiotoxicity in Patients Treated With Trastuzumab
Study Start Date : June 2007
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo
Drug: Placebo
Placebo, 32 mg, oral QD

Active Comparator: Candesartan
Drug: AT1 blocker candesartan
AT1 blocker candesartan, 32 mg oral QD

Primary Outcome Measures :
  1. The occurrence of cardiotoxicity, defined as a decline in LVEF (MUGA) of more than 15% or a decrease of less than 15% to an absolute value below 45%. [ Time Frame: during 1 year trastuzumab therapy and during 26 weeks after discontinuation of trastuzumab ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00459771

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Sponsors and Collaborators
The Netherlands Cancer Institute
Roche Pharma AG
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Principal Investigator: J.H.M. Schellens, MD PhD The Netherlands Cancer Institute
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: The Netherlands Cancer Institute Identifier: NCT00459771    
Other Study ID Numbers: M06HER
2006-001707-11 ( EudraCT Number )
First Posted: April 12, 2007    Key Record Dates
Last Update Posted: December 2, 2014
Last Verified: December 2014
Keywords provided by The Netherlands Cancer Institute:
angiotensin II-receptor (AT1) blocker
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action