Status:

COMPLETED

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

Lead Sponsor:

The Netherlands Cancer Institute

Collaborating Sponsors:

AstraZeneca

Roche Pharma AG

Conditions:

Breast Cancer

Eligibility:

FEMALE

18-79 years

Phase:

PHASE3

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 tra...

Detailed Description

Prospective, randomized pharmacological intervention study Primary objectives: \- to determine whether concurrent ATII-antagonist treatment can prevent trastuzumab-related cardiotoxicity, defined as...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

June 1 2007

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

December 1 2014

Estimated Enrollment :

210 Patients enrolled

Trial Details

Trial ID

NCT00459771

Start Date

June 1 2007

End Date

December 1 2014

Last Update

December 2 2014

Active Locations (19)

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Page 1 of 5 (19 locations)

1

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

2

Medisch Centrum Alkmaar

Alkmaar, Netherlands

3

Flevoziekenhuis

Almere Stad, Netherlands

4

The Netherlands Cancer Institute

Amsterdam, Netherlands, 1066 CX