Primary Objectives:Use 89Zr-Trastuzumab to characterise the in vivo biodistribution using PET imaging in the primary tumour and distant metastases.Comparie the uptake in patients with Her2/neu positive breast cancer to patients with HER2/neu…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Describe and quantify the 89Zirconium-Trastuzumab biodistribution in all
patients in terms of dose per volume (MBq/ml), percentage of injected dose per
volume tissue (%ID/ml) and Standardised Uptake Values (SUVs) based on the
PET/CT. This work will provide an insight into the tracer accumulation in
malignant and normal tissues with respect to mean accumulation and the
variation in accumulation patterns. Hence, this project will be used as a pilot
for a future larger study or, depending on the results, may serve as a
validation for the clinical application of this technique.
Secondary outcome
A description of the relation between uptake patterns on 18F-FDG and
89Zr-Trastuzumab PET/CT will be provided. Additionally, the variation serum
HER2 and Trastuzumab concentrations will be related to the Zr-89 Trastuzumab
accumulation in the normal liver tissue and tumour lesions. These data again
will provide mean and variation values in Her2/neu positive and negative
tumours.
Background summary
For patients with HER2/neu overexpressing or amplificated breast cancer,
Trastuzumab is the most import key of treatment. If we can visualise the amount
of 90-Zirconium-Trastuzumab tracer that binds the primary tumour, we could in
the future possibly predict the effectiveness of Trastuzumab therapy.
If discant metastases are present, the Trastuzumab therapy is meant to bind to
all the lesions to achieve an optimal treatment. The problem exists that
commonly used diagnostic modalities cannot discriminate between different
primary tumour or metastatis subtypes without a biopsy. If the distant
metastasis present is near an important organ or greater artery (aorta), it can
be a challenge or even life-threatning to attempt a biopsy. Therefore lesions
sometimes are left unclassified before treatment.
With the 89-Zirconium-Trastuzumab tracer it is possible to visualise on PET/CT
images which lesions binds the tracer and where it can be expected that the
treatment will be effective. If there are lesions present where the tracer
doesn't bind a different treatment can be chosen (chemotherapy, resection of
radiotherapy).
Study objective
Primary Objectives:
Use 89Zr-Trastuzumab to characterise the in vivo biodistribution using PET
imaging in the primary tumour and distant metastases.
Comparie the uptake in patients with Her2/neu positive breast cancer to
patients with HER2/neu negative breast cancer.
Secondary Objectives:
Compare the 89Zirconium tracer uptake within the primary tumour and metastases
with lesions visualised on the 18F-FDG PET/ CT.
Relate circulating HER2/neu (serum HER2) concentration to 89Zr-Trastuzumab
uptake in the tumour.
Study design
Patients with stadium II/III breast cancer with discant metastases visible on
18F-FDG PET/CT will be asked to participate in this study. A total of 12
patients will be included (8 with and 4 without HER2/neu amplification or
overexpression).
Two hours before administration of of het tracer veneus blood samples will be
taken for the measurement of circulating Trastuzumab after administration of a
preparation dose Trastuzumab (50 mg intravenously). A total dose of 37 MBq
89-Zirconium-Trastuzumab will be administered.
On the fourth day after adminstration of the tracer, a new venous bloodsample
will be taken for the measurement of circulating tracer directly followed by a
PET/CT acquisition in hanging prone- and in supine position, followed by a
prone position acquisition on a dedicated breast PET (MAMMI PET). On the sixth
day the venous blood sample will be followed solely by a PET/CT acquisition in
supine position.
On the Zirconium PET/CT the tracer accumulation will be quantified in all
lesions and in normal tissue (e.g. liver, blood pool and kidneys).
Study burden and risks
The participation in this study is not associated with significant risk for the
patient or personnel.
The participating patients will acquire a total dose of 20 mSv after the single
administration of 37 MBq 89-Zirconium-Trastuzumab and the two low-dose
(PET/)CT's. The radiation dose is comparable to 2 abdominal contrast enhanced
CT scans or 3 FDG PET/CT scan acquisitions.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
Histological confirmed breast cancer (8 with and 4 without HER2/neu overexpression or amplification), with a primary tumour and at least 1 distant metastatic lesion.;Recent diagnostic 18F-FDG PET/CT (less than 1 month old) made at the NKI-AvL.
Exclusion criteria
A medical condition (e.g. Li-Fraumeni) that would place the patient at unusual risk for development of new malignancies due to radiation.
Concurrent use of investigational drug with unknown biodistribution.
Present pregnancy, or the patient refuses to use an adequate contraception method if pre-menopausal.
Known allergy for murine proteins (present in Trastuzumab).
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 |
|---|---|
| EudraCT | EUCTR2014-002800-25-NL |
| CCMO | NL49980.031.14 |