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

NCT00459771 | Completed Phase 3 DMC

• 2 other identifiers: M06HER2006-001707-11
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 19

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.

Conditions

Breast Cancer

Keywords

angiotensin II-receptor (AT1) blocker; prevention; trastuzumab; cardiotoxicity

Outcome Measures

Primary Outcomes (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%.

  during 1 year trastuzumab therapy and during 26 weeks after discontinuation of trastuzumab

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Candesartan

ACTIVE COMPARATOR

Candasartan

Drug: AT1 blocker candesartan

Interventions

AT1 blocker candesartan DRUG

AT1 blocker candesartan, 32 mg oral QD

Candesartan

Placebo DRUG

Placebo, 32 mg, oral QD

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• AstraZeneca: collaborator
• Roche Pharma AG: collaborator

Study Sites (19)

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

Location

Medisch Centrum Alkmaar

Alkmaar, Netherlands

Location

Flevoziekenhuis

Almere Stad, Netherlands

Location

The Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands

Location

Slotervaart Hospital

Amsterdam, Netherlands

Location

Wilhelmina Ziekenhuis

Assen, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

Martini Ziekenhuis

Groningen, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Ziekenhuis de Tjongerschans

Heerenveen, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

Location

Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Canisius-Wilhelmina Hospital

Nijmegen, Netherlands

Location

UMC St. Radboud

Nijmegen, Netherlands

Location

VieCuri Medisch Centrum voor Noord-Limburg

Venlo, Netherlands

Location

Streekziekenhuis Koningin Beatrix

Winterswijk, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

Related Publications (1)

• Boekhout AH, Gietema JA, Milojkovic Kerklaan B, van Werkhoven ED, Altena R, Honkoop A, Los M, Smit WM, Nieboer P, Smorenburg CH, Mandigers CM, van der Wouw AJ, Kessels L, van der Velden AW, Ottevanger PB, Smilde T, de Boer J, van Veldhuisen DJ, Kema IP, de Vries EG, Schellens JH. Angiotensin II-Receptor Inhibition With Candesartan to Prevent Trastuzumab-Related Cardiotoxic Effects in Patients With Early Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2016 Aug 1;2(8):1030-7. doi: 10.1001/jamaoncol.2016.1726.

  PMID: 27348762 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Study Officials

• J.H.M. Schellens, MD PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2007
• First Posted: April 12, 2007
• Study Start: June 1, 2007
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2014
• Last Updated: December 2, 2014

Record last verified: 2014-12

Locations

NL (19)