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

This study has been completed.
Roche Pharma AG
Information provided by (Responsible Party):
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
First received: April 11, 2007
Last updated: December 1, 2014
Last verified: December 2014
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 Intervention Phase
Breast Cancer
Drug: AT1 blocker candesartan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Further study details as provided by The Netherlands Cancer Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 210
Study Start Date: June 2007
Study Completion Date: December 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Drug: Placebo
Placebo, 32 mg, oral QD
Active Comparator: Candesartan
Drug: AT1 blocker candesartan
AT1 blocker candesartan, 32 mg oral QD

  Show Detailed Description


Ages Eligible for Study:   18 Years to 79 Years
Genders 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459771

Medisch Centrum Alkmaar
Alkmaar, Netherlands
Almere, Netherlands
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands
Slotervaart Hospital
Amsterdam, Netherlands
The Netherlands Cancer Institute
Amsterdam, Netherlands, 1066 CX
Wilhelmina Ziekenhuis
Assen, Netherlands
Jeroen Bosch Hospital
Den Bosch, Netherlands
Deventer Ziekenhuis
Deventer, Netherlands
Medisch Spectrum Twente
Enschede, Netherlands
University Medical Center Groningen
Groningen, Netherlands
Martini Ziekenhuis
Groningen, Netherlands
Ziekenhuis de Tjongerschans
Heerenveen, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, Netherlands
Antonius Ziekenhuis
Nieuwegein, Netherlands
Canisius-Wilhelmina Hospital
Nijmegen, Netherlands
UMC St. Radboud
Nijmegen, Netherlands
VieCuri Medisch Centrum voor Noord-Limburg
Venlo, Netherlands
Streekziekenhuis Koningin Beatrix
Winterswijk, Netherlands
Isala Klinieken
Zwolle, Netherlands
Sponsors and Collaborators
The Netherlands Cancer Institute
Roche Pharma AG
Principal Investigator: J.H.M. Schellens, MD PhD The Netherlands Cancer Institute
  More Information

No publications provided

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT00459771     History of Changes
Other Study ID Numbers: M06HER, 2006-001707-11
Study First Received: April 11, 2007
Last Updated: December 1, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by The Netherlands Cancer Institute:
angiotensin II-receptor (AT1) blocker

Additional relevant MeSH terms:
Angiotensin II
Candesartan cilexetil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Antineoplastic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on November 25, 2015