Trial Title:
[68Ga]Ga-ABY-025 PET for Quantification of HER2-status in Solid Tumors
NCT ID:
NCT05619016
Condition:
Esophageal Neoplasms
Gastric Neoplasms Malignant
Breast Cancer
HER2-positive Gastric Cancer
Conditions: Official terms:
Neoplasms
Stomach Neoplasms
Esophageal Neoplasms
Conditions: Keywords:
68-Ga ABY-025
HER2 PET
PET/CT
Gastroesophageal cancer
Metastatic breast cancer
HER2 low
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Prospective, single-center, single-blinded, diagnostic explorative phase II basket trial.
Investigators select subjects that are scheduled for anti-HER2 treatment due to
- metastatic HER2 positive gastroesophageal cancer (GEAC)
- metastatic breast cancer with low HER2 expression (HER2low mBC).
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.
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Masking description:
Treating clinicians will be blinded for the results of the HER2-PET
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
[68Ga]Ga-ABY-025 PET
Description:
[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.
Arm group label:
Patients with HER2 positive GEAC or HER2 low cancer (pilot)
Other name:
HER2 PET
Intervention type:
Diagnostic Test
Intervention name:
Biopsy and analysis of HER2 expression
Description:
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.
Arm group label:
Patients with HER2 positive GEAC or HER2 low cancer (pilot)
Summary:
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).
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years.
2. The subject has given written consent to participate in the study.
3. Patients with metastatic disease because of gastroesophageal adenocarcinoma or
HER2-low breast cancer. Cohort 1: Histologically confirmed HER2-positive primary
gastroesophageal adenocarcinoma, scheduled for palliative HER2-targeted therapy;
Cohort 2: HER2-low metastatic breast cancer first within a pilot study (of which
five patients with de novo HER2-low mBC and five patients with pre-treated HER2-low
mBC). Later, within a post-pilot study. Definition of HER2 positivity (ASCO College
of American Pathologist 2018. HER2 Testing for Breast Cancer Guidelines.) HER2-low
mBC is defined as IHC 1+ or IHC 2+ but ISH negative.
4. At least one metastatic lesion ≥ 10 mm is available for biopsy defined on CT.
5. At least one (and up to five) additional metastatic index lesion/s ≥ 10 mm for
evaluation of treatment effect
6. World Health Organization (WHO) performance status ≤ 2.
7. Expected survival > 12 weeks.
Exclusion Criteria:
1. Significantly impaired renal function (GFR <30 ml/min/1.73 m2)
2. Allergy to iodinated contrast media
3. Subjects that for some reason are unable to exercise their rights, such as cognitive
function impairment.
4. Other manifest malignancy except for basal cell carcinoma of the skin.
5. 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.
6. 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.
7. 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.
8. 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.
9. Patients with increased risk of complications from biopsies, i.e. increased risk of
bleeding, defined as
- prothrombin time test (INR value) >1.4, platelet count <70 (109/l), activated
partial thromboplastin time (APTT) >30s.
- known bleeding disorder such as hemophilia, von Willebrand disease or platelet
disorders.
- any anticoagulants or antiplatelet treatment (except for low-dose
acetyl-salicylic acid (ASA), i. e 75 mg daily).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Radiation Physics and Nuclear Medicine, Karolinska University Hospital
Address:
City:
Stockholm
Zip:
14186
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Rimma Axelsson, Prof
Phone:
+46858580000
Email:
rimma.axelsson@ki.se
Contact backup:
Last name:
Siri af Burén, MD
Phone:
+46739099570
Email:
siri.afburen@regionstockholm.se
Investigator:
Last name:
Rimma Axelsson, Professor
Email:
Principal Investigator
Investigator:
Last name:
Renske Althena, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Magnus Nilsson, Professor
Email:
Sub-Investigator
Start date:
November 23, 2022
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Karolinska University Hospital
Agency class:
Other
Source:
Karolinska University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05619016
