We intend to study the effect of trastuzumab on the cardiac neuronal activity in patients with HER-2 positive breast cancer by using iodine-123 meta-iodobenzylguanidine (123I-MIBG) and cardiac imaging. 123I-MIBG, an analogue of the false…
ID
Source
Brief title
Condition
- Heart failures
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this pilot study is to assess the neuroadrenergic
system in patients with cardiac toxicity due to trastuzumab in order to reveal
the pathofysiological mechanisms of trastuzumab induced cardiotoxicity
Secondary outcome
The secondary objective of this study is, in case of a positive tendens of
abnormal I-MIBG scans in patients with declined LEVFs, to set up a prospective
randomized controlled trial for patients with trastuzumab induced cardiotoxiciy
in the future.
Background summary
Trastuzumab is a humanized monoclonal antibody directed against the human
epidermal growth factor receptor-2 (HER-2), also known as ErbB-2 or NEU, and
inhibits HER2-mediated malignant transformation. Amplification or
overexpression of HER-2 is seen in approximately 25% of invasive breast cancers
and is associated with a more aggressive form of cancer with an unfavorable
prognosis. However, cardiac toxicity is an important side effect of trastuzumab
therapy, which can manifest as symptomatic congestive heart failure (CHF) or
asymptomatic left ventricular ejection fraction (LVEF) decline. A higher
incidence of cardiotoxicity is seen in combination with high cummulative doses
of antracyclines, a common used type of cytotoxic drugs in breast cancer.
Cardiotoxicity due to trastuzumab differs from caardiotoxicty caused by
antracyclines. The pathofysiology of trastuzumab induced cardiotoxicity is
currently unknown. A hypotheses is that ,by blocking the HER-2 receptor,
signaling of the sympatovagal controle systems of the heart is impaired.
According to the interim analysis of the CARIT study, in the first three
patients, a scintigraphic evidence of cardiac sympathetic dysfunction was
observed. This is the reason for submitting this amendment where we extend the
patient population to include trastuzumab-treated breast cancer patients who
did not develop a significant reduction of the LVEF as a control group.
Study objective
We intend to study the effect of trastuzumab on the cardiac neuronal activity
in patients with HER-2 positive breast cancer by using iodine-123
meta-iodobenzylguanidine (123I-MIBG) and cardiac imaging. 123I-MIBG, an
analogue of the false neurotransmitter guanithidine, localizes in adrenergic
nerve terminals.
Study design
Retrospective, diagnostic, blinded, single center observationial/ diagnostic
pilot study
Study burden and risks
Unfortunately, the MUGA scan and I-MIBG scan cannot be done on the same day. So
the patient has to come to the LUMC twice. Both scans are well approved and
standard of care for certain indication. The MUGA scan is commonly used as a
diagnostic test for analysing the LVEF in patient, every 3 months during
therapy with trastuzumab and for many other indications. The scan takes about
45 minutes, the patient has to lay still which can be a burden. The
radiofarmaceuticals are well aproved, the radiation dose is low and not toxic.
The I MIBG scan is wel known for it's use in pateintes with heart failure. The
scan takes 45 minutes and has to be repeated after 4 hours. For this scan the
radiation exposure is low.
Postbus 9600, Postzone K1-P
2300 RC
NL
Postbus 9600, Postzone K1-P
2300 RC
NL
Listed location countries
Age
Inclusion criteria
•Adult patients with confirmed HER-2 positive breast cancer (immunohistochemistry score 3 or fluorescence in-situ hybridization positive) who have completed local regional therapy and treatment with trastuzumab or are still on treatment with trastuzumab.
•Permanent LVEF <=50% after treatment with trastuzumab, and/or
•A permanent relative decrease of >=10% from baseline measured by means of echocardiography or MUGA scan and confirmed after 3 weeks after/during treatment with trastuzumab, and/or
•Symptomatic congestive heart failure defined as NYHA class III/IV
•Age 18-80 years.
•Signed informed consent
•WHO 0-2
Amendement: Add control group: patients without a permanent relative decrease of >=10% from baseline measured by means of echocardiography or MUGA scan and confirmed after 3 weeks after/during treatment with trastuzumab, and/or symptomatic congestive heart failure defined as NYHA class III/IV
Exclusion criteria
•Pre-existing cardiac disease such as heart failure, ischemic and valvular heart disease, arrhythmia or poorly controlled hypertension.
•Concomitant inflammatory disease.
•Pregnancy/beast feeding.
•Allergy against radiopharmaceutical (99m Tc-based tracer) for MUGA scan.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL31280.058.10 |