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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-500448-39-00 | Other Identifier | EU CT Number |
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The goal of this phase II clinical trial is to improve the selection of patients with solid tumors who would benefit from effective treatment with HER2 targeted drugs. This will be achieved by examining patients with HER2 positive tumors in the esophagus or stomach or patients with advanced breast cancer with low HER2 expression (HER2low) with the HER2 specific positron emission tomography (PET) tracer ABY-025 (HER2-PET) and compare the imaging results with HER2 expression in tumor tissue derived from biopsies (reference standard).
The goal of this phase II interventional clinical trial is to evaluate the HER2-status in tumor lesions measured by Gallium-68-ABY-025-uptake on PET/CT with HER2-status defined by reference standard (laboratory analyses) in patients with gastroesophageal cancer (GEAC) and metastatic breast cancer with low HER2 expression (HER2-low mBC).
The participants in GEAC cohort of the study will undergo two sessions of HER2 PET and one 18-Fluorodeoxyglucose (18F-FDG) PET/CT for study purposes. The first HER2 PET is performed within 21 days before initiation of the systemic oncological treatment and is followed by tumor biopsies. A second HER2 PET and a second 18F-FDG PET will be performed adjacent to response evaluation after 3 courses of oncological therapy. Data from the PET investigations will be compared to HER2 expression analyses of the biopsy specimen and correlated to disease and survival data at follow up one year after inclusion. Within the pilot study, participants with HER2 low mBC will undergo one HER2 PET followed by biopsies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with HER2 positive GEAC or HER2 low cancer (pilot) | Experimental | The participants of the study will undergo two sessions of HER2 PET and one 18F-FDG PET/CT for study purposes. The first HER2 PET is performed within 21 days before initiation of the systemic oncological treatment including HER2-targeted drugs, and is followed by tumor biopsies. A second HER2 PET and a second 18F-FDG PET will be performed adjacent to response evaluation after 3 courses of oncological therapy. Data from the PET investigations will be compared to HER2 expression analyses of the biopsy specimen and correlated to disease and survival data at follow up one year after inclusion. Within the pilot study, participants with HER2 low mBC will undergo one HER2 PET followed by biopsies. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [68Ga]Ga-ABY-025 PET | Diagnostic Test | [68Ga]Ga-ABY-025 PET: Each patient in Cohort 1 will be imaged with a PET/CT twice using the radiolabeled investigational product ABY-025 as a tracer. At the time of injection, a 45-minutes long dynamic scan will take place over a pre specified region of interest. Three hours after injection a full body PET scan followed by a CT scan will be performed. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of HER2-positive lesions | Percentage of HER2-positive lesions (primary tumors and/or metastases) measured by tracer uptake on PET/CT which are also positive regarding HER2-status defined by reference biopsy-based standard used in clinical routine in patients with GEAC | up to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| SUV | Optimal Standardized Uptake Values (SUVs) cut-off values for separating HER2-positive/or HER2-low from HER2-negative lesions by reference standard methods. | up to 24 months |
| TBR | Tumor-to-Background Ratio (TBR) cut-off values for separating HER2-positive/or HER2-low from HER2-negative lesions by reference standard methods. |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment response 1 | To examine the change in HER2 expression measured by tracer uptake on PET/CT (SUVs and TBR) performed after 3 courses of chemotherapy/HER2 targeted drugs compared to pre-treatment values and in which proportion of the examined patients this occur. | up to 36 months |
| Treatment response 2 |
Inclusion Criteria:
Exclusion Criteria:
Significantly impaired renal function (GFR <30 ml/min/1.73 m2)
Allergy to iodinated contrast media
Subjects that for some reason are unable to exercise their rights, such as cognitive function impairment.
Other manifest malignancy except for basal cell carcinoma of the skin.
The patient presenting any contraindication for the use of HER2 targeted therapy for metastatic disease: congestive heart failure, baseline left ventricular ejection fraction (LVEF) less than 50%, transmural myocardial infarction, uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg), angina pectoris requiring medication, clinically significant valvular heart disease, high-risk arrhythmias, lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome, active gastrointestinal bleeding.
Inadequate organ function, suggested by the following laboratory results: absolute neutrophil count <1,500 cells/mm3, haemoglobin <90 g/L, total bilirubin ≥1.5 x Upper Limit of Normal (ULN) (unless the patient has documented Gilbert's syndrome), Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or Alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT) >5.0 x ULN.
Positive pregnancy test in women of childbearing potential (premenopausal or <12 months of amenorrhea post-menopause and who have not undergone surgical sterilization), or lactation.
Female patients of childbearing potential and sexually active and not willing to use a highly effective contraceptive. Examples of highly effective contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine devices (IUDs), and copper IUDs. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Women must refrain from donating eggs during this same period.
Patients with increased risk of complications from biopsies, i.e. increased risk of bleeding, defined as
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rimma Axelsson, Prof., MD | Contact | +46 8 585 800 00 | rimma.axelsson@ki.se | |
| Siri af Burén, MD | Contact | +46739099570 | siri.afburen@regionstockholm.se |
| Name | Affiliation | Role |
|---|---|---|
| Rimma Axelsson, Prof., MD | Karolinska University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Radiation Physics and Nuclear Medicine, Karolinska University Hospital | Recruiting | Stockholm | 14186 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30911434 | Background | Velikyan I, Schweighofer P, Feldwisch J, Seemann J, Frejd FY, Lindman H, Sorensen J. Diagnostic HER2-binding radiopharmaceutical, [68Ga]Ga-ABY-025, for routine clinical use in breast cancer patients. Am J Nucl Med Mol Imaging. 2019 Feb 15;9(1):12-23. eCollection 2019. | |
| 32201920 | Background | Alhuseinalkhudhur A, Lubberink M, Lindman H, Tolmachev V, Frejd FY, Feldwisch J, Velikyan I, Sorensen J. Kinetic analysis of HER2-binding ABY-025 Affibody molecule using dynamic PET in patients with metastatic breast cancer. EJNMMI Res. 2020 Mar 23;10(1):21. doi: 10.1186/s13550-020-0603-9. |
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| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D001706 | Biopsy |
| ID | Term |
|---|---|
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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Prospective, single-center, single-blinded, diagnostic explorative phase II basket trial.
Investigators select subjects that are scheduled for anti-HER2 treatment due to
All patients undergo a PET/CT with the interventional drug/radiotracer 68Ga-ABY-025 before starting treatment. GEAC patients will undergo an additional ABY-025-PET after 3 cycles of treatment. Results will be compared to HER2 analysis of tissue samples.
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Treating clinicians will be blinded for the results of the HER2-PET
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|
|
| Biopsy and analysis of HER2 expression | Diagnostic Test | Biopsy: Within 3 days after the first ABY-025-PET a tissue sample from at least one metastasis >10 mm available for biopsy, preferably shallow lymph nodes, will be analyzed for HER2 expression through immunohistochemistry- (IHC) and in situ hybridization- (ISH) analysis in patients with GEAC and HER2low mBC. |
|
| up to 24 months |
| Intra-individual heterogeneity of HER2-positivity | Percentage of tracer uptake sites on whole-body HER2 PET compared to all known cancer-related lesions, determined on the routine radiological investigation with CT as an estimation of intra-individual heterogeneity of HER2-positivity. | up to 24 months |
| Feasibility in HER2low | Percentage of false-negative findings on HER2 PET compared to results from immunohistochemistry testing (IHC) from at least one index lesion in patients with HER2-low mBC. | up to 24 months |
| HER2 positive cancer burden | Percentage of tracer uptake in sites, not previously determined on the routine radiological investigation with CT, as a measure of cancer burden determined on the whole body HER2 PET in tumor lesions. | up to 24 months |
| Safety aspects of ABY-025 | Frequency of Adverse Events (AEs), Adverse Reactions (ARs), Serious Adverse Events (SAEs), and Suspected Unexpected Serious Adverse Reactions (SUSARs). | up to 36 months |
Changes in SUVs in index lesions, as well as in the total HER2-positive tumor volume at HER2 PET (percentage) before and after treatment with systemic therapy including HER2 targeted drugs to evaluate treatment response. |
| up to 36 months |
| Comparison between HER2 PET and FDG PET | Comparison of treatment response evaluation performed by HER2 PET versus 18F-FDG PET/CT defined as percentage of complete and partial response, stable and progressive disease (percentage of concordant results). | up to 24 months |
| HER2 PET as a prognostic tool | The correlation between HER2 expression measured by a total HER2-positive tumor volume at HER2 PET before treatment and progression-free survival (PFS), overall (or clinical) response rate to systemic therapy (ORR) at 12 months after inclusion. | up to 36 months |
| HER2 PET as a marker for treatment related cardiotoxicity | The presence and frequency of myocardial uptake of [68Ga]Ga-ABY-025 and relation to treatment-related cardiotoxicity determined by echocardiography. | up to 36 months |
| Dynamic PET parameters | The agreement between whole body static imaging and kinetic parameters in the determination of HER2-status. | up to 36 months |
| 20554729 | Background | Ahlgren S, Orlova A, Wallberg H, Hansson M, Sandstrom M, Lewsley R, Wennborg A, Abrahmsen L, Tolmachev V, Feldwisch J. Targeting of HER2-expressing tumors using 111In-ABY-025, a second-generation affibody molecule with a fundamentally reengineered scaffold. J Nucl Med. 2010 Jul;51(7):1131-8. doi: 10.2967/jnumed.109.073346. Epub 2010 Jun 16. |
| 26912439 | Background | Sandstrom M, Lindskog K, Velikyan I, Wennborg A, Feldwisch J, Sandberg D, Tolmachev V, Orlova A, Sorensen J, Carlsson J, Lindman H, Lubberink M. Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients. J Nucl Med. 2016 Jun;57(6):867-71. doi: 10.2967/jnumed.115.169342. Epub 2016 Feb 9. |
| 24665085 | Background | Sorensen J, Sandberg D, Sandstrom M, Wennborg A, Feldwisch J, Tolmachev V, Astrom G, Lubberink M, Garske-Roman U, Carlsson J, Lindman H. First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule. J Nucl Med. 2014 May;55(5):730-5. doi: 10.2967/jnumed.113.131243. Epub 2014 Mar 24. |
| 26877784 | Background | Sorensen J, Velikyan I, Sandberg D, Wennborg A, Feldwisch J, Tolmachev V, Orlova A, Sandstrom M, Lubberink M, Olofsson H, Carlsson J, Lindman H. Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT. Theranostics. 2016 Jan 1;6(2):262-71. doi: 10.7150/thno.13502. eCollection 2016. |
| 20130858 | Background | Tolmachev V, Velikyan I, Sandstrom M, Orlova A. A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue. Eur J Nucl Med Mol Imaging. 2010 Jul;37(7):1356-67. doi: 10.1007/s00259-009-1367-7. Epub 2010 Feb 4. |
| 28261749 | Background | Sandberg D, Tolmachev V, Velikyan I, Olofsson H, Wennborg A, Feldwisch J, Carlsson J, Lindman H, Sorensen J. Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT. Eur J Nucl Med Mol Imaging. 2017 Aug;44(8):1337-1346. doi: 10.1007/s00259-017-3650-3. Epub 2017 Mar 6. |
| 38548353 | Derived | Altena R, Buren SA, Blomgren A, Karlsson E, Tzortzakakis A, Brun N, Moein MM, Jussing E, Frejd FY, Bergh J, Tran TA, Hartman J, Axelsson R. Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [68Ga]Ga-ABY-025: Results from a Pilot Study. J Nucl Med. 2024 May 1;65(5):700-707. doi: 10.2967/jnumed.123.266847. |
| 37991639 | Derived | Jussing E, Ferrat M, Moein MM, Alfredeen H, Tegnebratt T, Bratteby K, Samen E, Feldwisch J, Altena R, Axelsson R, Tran TA. Optimized, automated and cGMP-compliant synthesis of the HER2 targeting [68Ga]Ga-ABY-025 tracer. EJNMMI Radiopharm Chem. 2023 Nov 22;8(1):41. doi: 10.1186/s41181-023-00226-y. |
| D006258 |
| Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |