Molecular Imaging of HER2 Expression in Breast Cancer Using 99mTc-ZHER2.
Study Details
Study Description
Brief Summary
The study should evaluate distribution of 99mTc-ZHER2:41071 Affibody molecule in patients with primary HER2-positive and HER2-negative breast cancer
The primary objectives are:
-
To assess distribution of 99mTc-ZHER2:41071 in normal tissues and in tumors over time;
-
To evaluate dosimetry of 99mTc-ZHER2:41071;
-
To obtain initial information concerning safety and tolerability of 99mTc-ZHER2:41071 after single intravenous injection:
The secondary objectives are:
- To compare the tumor imaging data with the data concerning HER2 expression obtained by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) analysis of biopsy samples.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
Overall goal of the project: To determine HER2 expression level in primary breast cancer and possibly in axillary lymph node metastases before neoadjuvant targeted (trastuzumab or trastuzumab+pertuzumab) therapy.
Phase I. Distribution of 99mTc-ZHER2:41071 in patients with primary breast cancer.
The study should evaluate distribution of 99mTc-ZHER2:41071 in patients with primary HER2-positive and HER2-negative breast cancer.
The primary objectives are:
-
To assess distribution of 99mTc-ZHER2:41071 in normal tissues and in tumors over time;
-
To evaluate dosimetry of 99mTc-ZHER2:41071;
-
To obtain initial information concerning safety and tolerability of 99mTc-ZHER2:41071 after single intravenous injection:
The secondary objectives are:
- To compare the tumour imaging data with the concerning HER2 expression obtained by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) analysis of biopsy samples:
Methodology:
Open-label, exploratory, single center study. The subjects will receive a single injection of the labelled tracer.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: The tested injected doses of 99mTc-ZHER2:41071 500 μg At least five (5) evaluable subjects with HER2-positive status and at least five (5) subjects with HER2-negative status have to be enrolled in the study for each tested protein dose. Subjects withdrawn from the study for any reason will be replaced. |
Drug: SPECT
One single injection of 99mTc-ZHER2:41071, followed by gamma camera imaging after 2, 4, 6 and 24 hours.
|
| Experimental: The tested injected doses of 99mTc-ZHER2:41071 1000 μg At least five (5) evaluable subjects with HER2-positive status and at least five (5) subjects with HER2-negative status have to be enrolled in the study for each tested protein dose. Subjects withdrawn from the study for any reason will be replaced. |
Drug: SPECT
One single injection of 99mTc-ZHER2:41071, followed by gamma camera imaging after 2, 4, 6 and 24 hours.
|
Outcome Measures
Primary Outcome Measures
- Gamma camera-based whole-body 99mTc-ZHER2:41071 uptake value (% per organ) [24 hours]
Whole-body 99mTc-ZHER2:41071 uptake coinciding with normal organs and tissues will be assessed using gamma camera at 2, 4, 6 and 24 hours after injection and calculated as percentage (%) of the injected dose of the radiopharmaceutical
- SPECT/CT-based 99mTc-ZHER2:41071 uptake value in tumor lesions (kcounts)/SUV [6 hours]
99mTc-ZHER2:41071 focal uptake coinciding with tumor lesions will be assessed using SPECT/CT at 2, 4 and 6 hours after injection and measured in kcounts and SUV
- SPECT-based 99mTc-ZHER2:41071 background uptake value (kcounts)/SUV [6 hours]
Uptake of 99mTc-ZHER2:41071 in the regions without pathological findings will be assessed using SPECT/CT at 2, 4 and 6 hours after injection and measured in kcounts and SUV.
- Tumor-to-background ratio (SPECT) [6 hours]
The SPECT-based tumor-to-background ratio will be calculated as follows: the value of 99mTc-ZHER2:41071 uptake coinciding with tumor lesions (kcounts) will be divided by the value of 99mTc-ZHER2:41071 uptake coinciding with the regions without pathological findings (kcounts)
Secondary Outcome Measures
- Safety attributable to 99mTc-ZHER2:41071 injections (physical examination) [24 hours]
The safety attributable to 99mTc-ZHER2:41071 injections will be evaluated based on the assessments of physical examination (% of cases with abnormal findings relative to baseline)
- Safety attributable to 99mTc-ZHER2:41071 injections (vital signs) [24 hours]
The safety attributable to 99mTc-ZHER2:41071 injections will be evaluated based on the assessments of vital signs (% of cases with abnormal findings relative to baseline)
- Safety attributable to 99mTc-ZHER2:41071 injections (ECG ) [24 hours]
The safety attributable to 99mTc-ZHER2:41071 injections will be evaluated based on the assessments of ECG (% of cases with abnormal findings relative to baseline)
- Safety attributable to 99mTc-ZHER2:41071 injections (blood laboratory tests) [24 hours]
The safety attributable to 99mTc-ZHER2:41071 injections will be evaluated based on the blood laboratory tests (% of cases with abnormal findings relative to baseline)
- Safety attributable to 99mTc-ZHER2:41071 injections (urine laboratory tests) [24 hours]
The safety attributable to 99mTc-ZHER2:41071 injections will be evaluated based on the urine laboratory tests (% of cases with abnormal findings relative to baseline)
- Safety attributable to 99mTc-ZHER2:41071 injections (incidence and severity of adverse events) [24 hours]
The safety attributable to 99mTc- ZHER2:41071 injections will be evaluated based on the rate of adverse events (%)
- Safety attributable 99mTc-ZHER2:41071 injections (concomitant medication) [24 hours]
The safety attributable to 99mTc-ZHER2:41071 injections will be evaluated based on the rate of administration of concomitant medication (%)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subject is > 18 years of age
-
Diagnosis of primary breast cancer with possible lymph node metastases
-
Availability of results from HER2 status previously determined on material from the primary tumor, either
-
HER2-positive, defined as a DAKO HercepTest™ score of 3+ or FISH positive or
-
HER2-negative, defined as a DAKO HercepTest™ score of 0 or 1+; or else if 2+ then FISH negative
-
Volumetrically quantifiable tumour lesions on CT or MRI, with at least one lesion > 2.0 cm in greatest diameter outside of the liver and kidneys
-
Hematological, liver and renal function test results within the following limits:
-
White blood cell count: > 2.0 x 109/L
-
Hemoglobin: > 80 g/L
-
Platelets: > 50.0 x 109/L
-
ALT, ALP, AST: =< 5.0 times Upper Limit of Normal
-
Bilirubin =< 2.0 times Upper Limit of Normal
-
Serum creatinine: Within Normal Limits
-
A negative pregnancy test for all patients of childbearing potential. Sexually active women of childbearing potential participating in the study must use a medically acceptable form of contraception for at least 30 days after study termination
-
Subject is capable to undergo the diagnostic investigations to be performed in the study
-
Informed consent
Exclusion Criteria:
-
Second, non-breast malignancy
-
Active current autoimmune disease or history of autoimmune disease
-
Active infection or history of severe infection within the previous 3 months (if clinically relevant at screening)
-
Known HIV positive or chronically active hepatitis B or C
-
Administration of other investigational medicinal product within 30 days of screening
-
Ongoing toxicity > grade 2 from previous standard or investigational therapies, according to US National Cancer Institute's
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | TomskNRMC | Tomsk | Russian Federation |
Sponsors and Collaborators
- Tomsk National Research Medical Center of the Russian Academy of Sciences
Investigators
- Principal Investigator: Vladimir Chernov, MD, Prof., Tomsk NRMC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 99mTc-ZHER2