In this feasibility study, we will validate the value of the preoperative [89Zr]trastuzumab PET/CT imaging to identify HER2 positive primary breast cancer and the possibility to predict pathological complete response.
ID
Source
Brief title
Condition
- Breast disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine if HER2 positive primary breast cancer can be detected by
[89Zr]trastuzumab PET/CT imaging, using histopathological examination as the
gold standard, after neoadjuvant treatment.
- Assess the negative predictive value and sensitivity of [89Zr]trastuzumab
PET/CT imaging to detect HER2 positive primary breast cancer.
Secondary outcome
- Assess agreement between [89Zr]trastuzumab PET/CT-imaging signal in the tumor
and axilla, histopathologic evidence of tumor and HER2 expression.
- Assess the agreement between different imaging modalities ([89Zr]trastuzumab
PET/CT-scan, [18F]FDG-PET/CT and MRI).
Background summary
Currently, there is no adequate non-invasive diagnostic modality to assess
treatment response after neoadjuvant therapy in breast cancer patients. To
adequately predict histological complete response, further optimization of
non-invasive imaging approaches for response monitoring is crucial. For
patients with a complete response to neoadjuvant treatment non-operative
treatment might be an option.
Approximately 20% of breast cancers have an overexpression of the human
epidermal growth factor receptor 2 (HER2), which can be selectively targeted by
the monoclonal antibody trastuzumab (Herceptin, Genentech, San Francisco, USA).
By labelling trastuzumab with a radiotracer ([89Zr]trastuzumab) preoperative
imaging using positron emission tomography (PET/CT) is possible.
Study objective
In this feasibility study, we will validate the value of the preoperative
[89Zr]trastuzumab PET/CT imaging to identify HER2 positive primary breast
cancer and the possibility to predict pathological complete response.
Study design
This pilot study is a phase II, multicenter study in HER2 positive breast
cancer patients. This study will assess the feasibility of detection of HER2
positive breast cancer by preoperative [89Zr]trastuzumab PET/CT imaging of the
primary tumor. For this study 20 patients with HER2 positive breast cancer will
be included. All patients will undergo standard-of-care treatment, with
additionally pre- and after neoadjuvant chemotherapy [89Zr]trastuzumab PET/CT
imaging. All patients will receive 50 mg [89Zr]trastuzumab 4 days prior to the
pre-neoadjuvant [89Zr]trastuzumab PET/CT scan and 4 days prior to the
post-neoadjuvant [89Zr]trastuzumab PET/CT scan. The negative predictive value
and sensitivity of HER2-targeting PET will be determined. Validation will take
place by histopathologic assessment of tissue to determine the presence (or
absence) of tumor tissue and immunohistochemically assessment for tumor HER2
expression.
Study burden and risks
The risk for the individual patients is the risk of the use of ionizing
radiation, incidental PET findings and (so far unknown) possible adverse
effects of [89Zr]trastuzumab. Interference with standard clinical care is not
expected.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
• Female patients aged 18 years or older.
• Confirmed diagnosis of HER2 positive primary breast cancer (confirmed by
immunohistochemical staining of preoperative core-needle biopsy of tumor
tissue; IHC with strong intensity 3+ or fluorescence in situ hybridization
(FISH)) and eligible for breast cancer surgery.
• Tumor size >= 5 mm (0.5 cm) diameter according to anatomical imaging data.
• WHO performance score 0-2.
• Patients planned for neoadjuvant therapy.
• Female patients need to be either surgically sterile, post-menopausal or
pre-menopausal and not pregnant. Pre-menopausal female patients who are not
surgically sterile should also employ an effective method of birth control for
at least one month post-dosing when it consists of a hormonal contraceptive
method or IUD. For other contraceptive methods, premenopausal females who are
not surgically sterile have to agree to use an effective method of
contraception.
• Absence of any psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol and
follow-up schedule; those conditions should be discussed with the patient
before registration in the trial.
• Before patient registration, written informed consent must be given according
to ICH/GCP, and national/local regulations.
Exclusion criteria
• Any condition that in the opinion of the investigator could potentially
jeopardize the health status of the patient.
• Medical or psychiatric conditions that compromise the patient*s ability to
give informed consent. Presence of any psychological, familial, sociological or
geographical condition potentially hampering compliance with the study protocol
and follow-up schedule.
• Prior radiotherapy to the targeted breast.
• Breast prosthesis in the target breast.
• Unacceptable known (clinical significant) cardiovascular or pulmonary
disease, renal or liver dysfunction.
• Known hypersensitivity to drugs comparative to trastuzumab or drugs in the
same class (immunoglobulins), or any of their excipients or to any component of
[89Zr]trastuzumab.
• Concomitant medication known to interact with trastuzumab.
• Inability to undergo PET/CT scanning (e.g. claustrophobia, weight limits or
inability to tolerate lying for the duration of an PET/CT scan (~30 min)).
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 |
|---|---|
| EudraCT | EUCTR2018-004247-23-NL |
| CCMO | NL68188.058.18 |