Clinical trial NCT01016886: Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research
Official title: A Prospective Study to See if Cardiac Effects of Herceptin Can be Prevented With Standard Heart Medications
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Heart Failure
Keywords: trastuzumab
cardiac MRI
beta-blocker
biomarkers
angiotensin converting enzyme inhibitor
cardiotoxicity
HER2 positive
Lead sponsor: AHS Cancer Control Alberta
Sponsor class: OTHER
First posted: 2009-11-20
Enrollment: 99
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: While trastuzumab has been shown to prevent recurrences of breast cancer, some women may also experience damage to their heart muscle (including heart failure) as a result of their treatment. The investigators hope to learn if standard medications used in heart failure can prevent heart damage caused by trastuzumab in women with breast cancer. The investigators would also like to know if there are any ways to detect this damage earlier using magnetic resonance imaging (MRI) and blood tests.

Detailed description: We propose a randomized, placebo-controlled, double-blind study evaluating the efficacy of an ACE-inhibitor (perindopril) or a beta blocker (bisoprolol) for the prevention of LV remodeling among women with early breast cancer scheduled for chemotherapy and one year of trastuzumab. Participants will undergo cardiac MRI at baseline and 3 and 12 months, replacing the usual MUGA, as well as a post-treatment cardiac MRI at 24 months to evaluate long-term effect.

Eligibility criteria: Inclusion Criteria:

* Histologic diagnosis of HER2 positive breast carcinoma
* Eligible to receive trastuzumab
* Age \> 18 years
* Able to give informed consent
* No contraindications to MRI

Exclusion Criteria:

* Known contraindication to beta-blocker therapy
* Known contraindication to ACEI therapy
* Current treatment with ACEI or beta blocker for other indication
* History of heart failure, cardiomyopathy or baseline LVEF \< 50%

Primary outcomes:
measure: The primary objective is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular (LV) remodeling among women with HER2+ early breast cancer.
timeFrame: 3.5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta/ Cross Cancer Institute
state: Alberta
Study officials:
affiliation: Alberta Health services
name: Ian Paterson, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haykowsky MJ, Mackey JR, Thompson RB, Jones LW, Paterson DI. Adjuvant trastuzumab induces ventricular remodeling despite aerobic exercise training. Clin Cancer Res. 2009 Aug 1;15(15):4963-7. doi: 10.1158/1078-0432.CCR-09-0628. Epub 2009 Jul 21.
citation: Pituskin E, Haykowsky M, Mackey JR, Thompson RB, Ezekowitz J, Koshman S, Oudit G, Chow K, Pagano JJ, Paterson I. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101--Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI. BMC Cancer. 2011 Jul 27;11:318. doi: 10.1186/1471-2407-11-318.