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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2010 by The Netherlands Cancer Institute.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
AstraZeneca
Roche Pharma AG
Information provided by:
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT00459771
First received: April 11, 2007
Last updated: July 29, 2010
Last verified: July 2010
  Purpose

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 ]

Estimated Enrollment: 200
Study Start Date: June 2007
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo, 32 mg, oral QD
Other Name: Placebo
Active Comparator: Candesartan
Candasartan
Drug: AT1 blocker candesartan
AT1 blocker candesartan, 32 mg oral QD
Other Name: AT1 blocker candesartan

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  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

Contacts
Contact: J.H.M. Schellens, MD PhD +31 20 512 2446 j.slijkerman@nki.nl
Contact: A. Boekhout + 31 20 512 1035 a.boekhout@nki.nl

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, MA 02215
Contact: J. D. Chang, MD         
Principal Investigator: J. D. Chang, MD         
Netherlands
Medisch Centrum Alkmaar Recruiting
Alkmaar, Netherlands
Contact: C. H. Smorenburg, MD, PhD         
Principal Investigator: C. H. Smorenburg, MD, PhD         
Flevoziekenhuis Recruiting
Almere, Netherlands
Contact: V. Lustig, MD         
Principal Investigator: V. Lustig, MD         
The Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: J.H.M. Schellens, MD, PhD         
Principal Investigator: J.H.M. Schellens, Prof. MD.         
Slotervaart Hospital Recruiting
Amsterdam, Netherlands
Contact: M. Soesan, MD         
Principal Investigator: M. Soesan, MD, PhD         
Onze Lieve Vrouwe Gasthuis Recruiting
Amsterdam, Netherlands
Contact: B. de Valk, MD         
Principal Investigator: B. de Valk, MD         
Wilhelmina Ziekenhuis Recruiting
Assen, Netherlands
Contact: P. Nieboer, MD, PhD         
Principal Investigator: P. Nieboer, MD, PhD         
Jeroen Bosch Hospital Recruiting
Den Bosch, Netherlands
Contact: T. Smilde, MD, PhD         
Principal Investigator: T. Smilde, MD, PhD         
Deventer Ziekenhuis Recruiting
Deventer, Netherlands
Contact: L. Kessels, MD, PhD         
Principal Investigator: L. Kessels, MD, PhD         
Medisch Spectrum Twente Recruiting
Enschede, Netherlands
Contact: W. Smit, MD, PhD         
Principal Investigator: W. Smit, MD, PhD         
Martini Ziekenhuis Recruiting
Groningen, Netherlands
Contact: A.W.G. van der Velde, MD         
Principal Investigator: A.W.G. van der Velde, MD         
University Medical Center Groningen Recruiting
Groningen, Netherlands
Contact: E.G.E. de Vries, MD PhD         
Principal Investigator: E.G.E. de Vries, Prof. MD.         
Ziekenhuis de Tjongerschans Recruiting
Heerenveen, Netherlands
Contact: J. de Boer, MD         
Principal Investigator: J. de Boer, MD         
Medisch Centrum Leeuwarden Recruiting
Leeuwarden, Netherlands
Contact: W.E. Fiets, MD, PhD         
Principal Investigator: W.E. Fiets, MD, PhD         
Antonius Ziekenhuis Recruiting
Nieuwegein, Netherlands
Contact: M. Los, MD         
Principal Investigator: M. Los, MD         
Canisius-Wilhelmina Hospital Recruiting
Nijmegen, Netherlands
Contact: C.M.P.W. Mandigers, MD, PhD         
Principal Investigator: C.M.P.W. Mandigers, MD, PhD         
UMC St. Radboud Recruiting
Nijmegen, Netherlands
Contact: P B. Ottevanger, MD, PhD         
Principal Investigator: P. B. Ottevanger, MD, PhD         
VieCuri Medisch Centrum voor Noord-Limburg Recruiting
Venlo, Netherlands
Contact: A. J. van der Wouw, MD, PhD         
Principal Investigator: A. J. van der Wouw, MD, PhD         
Streekziekenhuis Koningin Beatrix Recruiting
Winterswijk, Netherlands
Contact: P.P.J.B.M.M. Schiphorst, MD         
Principal Investigator: P.P.J.B.M.M. Schiphorst, MD         
Isala Klinieken Recruiting
Zwolle, Netherlands
Contact: A. Honkoop, MD PhD         
Principal Investigator: A. Honkoop, MD, PhD         
Sponsors and Collaborators
The Netherlands Cancer Institute
AstraZeneca
Roche Pharma AG
Investigators
Principal Investigator: J.H.M. Schellens, MD PhD The Netherlands Cancer Institute
  More Information

No publications provided

Responsible Party: S. Rodenhuis, Prof. MD, NKI-AVL
ClinicalTrials.gov Identifier: NCT00459771     History of Changes
Other Study ID Numbers: M06HER, 2006-001707-11
Study First Received: April 11, 2007
Last Updated: July 29, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Angiotensin II
Candesartan
Candesartan cilexetil
Trastuzumab
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 October 21, 2014