The aim of this study is to investigate in patients with metastatic HER2 positive or HER2-low breast cancer whether a PET scan with a new HER2 tracer ([89Zr] DFO*trastuzumab) accurately depicts all abnormalities and whether ultimately this HER2 PET…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Biodistribution: 89Zr-DFO*-trastuzumab uptake (standard uptake values
(SUVmean, %ID/kg) in normal organs/tissues and bloodpool.
- Biodistribution as above from historical controls with HER2+ breast cancer (n
= 20) who underwent 89Zr-trastuzumab PET imaging.
Secondary outcome
- Tumor uptake: 89Zr-DFO*-trastuzumab uptake (SUV, %ID/kg) in tumor lesions.
- Tumor uptake as above in historical controls with HER2+ breast cancer (n =
20) who underwent 89Zr-trastuzumab PET imaging.
- Whole blood and plasma PK of 89Zr-DFO*-trastuzumab
- Image-derived PK for 89Zr-DFO*-trastuzumab
- Literature-derived PK for unlabelled trastuzumab
- Visual PET imaging analysis of tumor uptake of 89Zr-DFO*-trastuzumab and
89Zr-trastuzumab.
- Tumor-to-blood ratio of 89Zr-DFO*-trastuzumab (whole blood and plasma as well
as image derived)
- Tumor-to-image derived blood uptake ratio of 89Zr-trastuzumab
- HER2 expression measured by IHC on tumor biopsies
Background summary
Different forms of breast cancer are known. On the surface, the cancer cells
can have different properties (receptors), which promote the growth of these
cells. In 20% of these tumors, the "human epidermal growth factor receptor 2"
(HER2) is found on the surface of the cells. Nowadays, there are many drugs
available to block this growth. In case of a HER2 positive tumor, trastuzumab
(Herceptin®) is often prescribed, sometimes in combination with chemotherapy.
This is mostly not the case with HER2-low.
In order to choose the right treatment for the patient, it is therefore of
great importance to know whether HER2 is present on the cancer cells. Over
time, however, HER2 may disappear or emerge. This makes it even more important
to have up-to-date information about the presence of HER2 in the metastases. In
this way, it can be prevented that patients receive too much or too little
treatment.
To find out whether metastases have HER2, tissue biopsy of a metastasis must be
done. Despite the fact that the biopsy provides important information, only one
metastasis is investigated. But not all metastases need to have the same
properties. That is why we do research on scans that show all places in the
body where HER2 is present. By using the detection agent for HER2 (=
radioactive trastuzumab, or [89Zr]-DFO*trastuzumab) at different times after
administration, we can better understand how radioactive trastuzumab binds to
HER2. In this way we hope to obtain additional information about the presence
of HER2 from all metastases.
Study objective
The aim of this study is to investigate in patients with metastatic HER2
positive or HER2-low breast cancer whether a PET scan with a new HER2 tracer
([89Zr] DFO*trastuzumab) accurately depicts all abnormalities and whether
ultimately this HER2 PET scan can be used to predict response to treatment.
Study design
During the 1st visit, radioactive trastuzumab will be administered. For
administration, 2 infusion needles are inserted - one into each arm. Blood will
be taken via one IV while the other IV is used to administer the radioactive
trastuzumab into the bloodstream. In a period of 2 hours after administration,
4 vials of blood will be taken. In the first three patients, a PET scan will be
made 1 hour after administration.
The 2nd visit follows 1 day later where a PET scan is made and 1 vial of blood
is taken
The 3rd visit follows 4 days after the administration of radioactive
trastuzumab in which a PET scan is made and 1 vial of blood is taken
The 4th visit follows 6 days after the administration of radioactive
trastuzumab in which a PET scan is made and 1 vial of blood is taken
Intervention
Biopsy of the primary tumour or a metastasis to confirm HER-status. Applicible
only if the most recent biopsy is more than 16 weeks old, or if in that
timeframe a therapy switch occured.
Study burden and risks
The study requires 4 additional hospital visits. 2 IVs are placed and blood
samples will be taken at 7 different timepoints (of which 3x by means of an
extra venipuncture). It is possible that people may experience local pain
complaints. The scans are made after the injection of radioactive trastuzumab.
For the (three or four) scans, patients must lie supine for 60 minutes each
time. We use radioactive materials and X-rays for the scans. The total
additional radiation exposure in this study is a maximum of 24 mSv.
A biopsy may be uncomfortable. Risks associated are bleeding, infection, pain
and neurological damage.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Patients with:
- HER2+ or HER2-low breast cancer with metastatic disease,
- and starting systemic therapy or having stable, RECIST measurable disease
(with or without treatment).
• A recent (< 16 weeks of start of study) biopsy confirming HER2-status, as
long as no therapy changes took place within those 16 weeks.
• Able to undergo PET imaging procedures.
• At least one lesion of at least 1.5 cm amenable for PET imaging
• Age >18 years of age, willing and able to comply with the protocol as judged
by the investigator.
• Signed written informed consent.
• Have a World Health Organisation (WHO) performance status of 0-2.
• Life expectancy of > 3 months.
• Have measurable disease based on RECIST 1.1.
• Adequate organ and bone marrow function, as deemed acceptable by the treating
physician
Exclusion criteria
• Contraindications for systemic treatment (as will be assigned by treating
physician).
• Pregnant or lactating women.
• Prior allergic reaction to immunoglobulins or immunoglobulin allergy.
• Inability to comply with study procedures.
• Has substance abuse or any other medical conditions such as clinically
significant cardiac or psychological conditions, that may, in the opinion of
the investigator, interfere with the subject*s participation in the clinical
study or evaluation of the clinical study results.
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 | EUCTR2022-003120-40-NL |
| ClinicalTrials.gov | NCT05955833 |
| CCMO | NL82608.018.22 |