Study to Evaluate Safety and Dosimetry of [18F]GEH121224 in Patients With Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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The study described in this protocol is a Phase 1, single center clinical trial to evaluate the safety and potential of [18F]GEH121224 as a PET radiotracer for the diagnostic imaging of HER2 positive breast cancer lesions. A group of 6 patients will be selected to perform a dosimetry study with [18F]GEH121224 followed by another group of 6 patients in a test-retest study. The results of this study will provide crucial information to guide the development of [18F]GEH121224 for the detection of HER2 status in advanced breast cancer patients. This study will use established methods for characterizing the radiation dosimetry, biodistribution and basic pharmacokinetics of a radiotracer.

Detailed Description
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Group 1 : Six female patients with locally advanced or metastatic breast cancer and with HER2-positive primary tumor status will be included. These patients will receive a single injection of GEH121224 (18F) Injection and will then undergo a dynamic whole-body PET/CT scan starting at the time of injection (8 sequential scans over 90 minutes anticipated) followed by static whole-body scans starting at 120 minutes and 240 minutes after injection. Blood samples will be collected at specified time points during imaging for pharmacokinetic analysis. Safety and imaging data will be reviewed on an ongoing basis after dosing of each patient in Group 1. The injected activity may be adjusted for subsequent patients in Group 1 based on this review. A complete aggregate review of safety and imaging data will be performed by the Sponsor once all 6 patients in Group 1 have been dosed. If no safety concerns are raised, enrollment into Group 2 will start. The injected radioactivity may also be optimized before enrolling patients in Group 2. Review of safety data is described in the Safety Data Review Plan. Group 2 : Six female patients with locally advanced or metastatic breast cancer and with HER2-positive primary tumor status will be included in Group 2 and will receive a single injection of GEH121224 (18F) Injection on each of 2 separate days. On Imaging Day 1, patients will receive a single injection of GEH121224 (18F) Injection and will then undergo [18F]GEH121224 PET imaging at the optimal scan time identified in Group 1. Within 3 weeks (3 to 21 days; Imaging Day 2), patients will receive a second single injection of GEH121224 (18F) Injection and again undergo [18F]GEH121224 PET imaging at the optimal scan time identified in Group 1. Patient safety will be monitored throughout the course of the study, including a 24-hour safety follow-up by phone after each dose of [18F]GEH121224.

Official Title
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A Phase 1 Study to Assess the Safety, Radiation Dosimetry and Biodistribution, and Basic Pharmacokinetics of [18F]GEH121224 and Determine the Optimal Timing of Imaging in Patients With Locally Advanced or Metastatic Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: GEH121224 (18F) Injection
* Diagnostic Test: Dynamic and Static - PET/CT Scan
* Diagnostic Test: Static - PET/CT Scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients aged ≥18 years Willingness and ability to comply with study procedures and signed and dated informed consent For women of child-bearing potential, negative urine pregnancy test at screening and o on the day of investigational medicinal product (IMP) administration (with the result known before IMP administration) and willingness to use contraception (barrier, abstinence, non-hormonal) for 3 weeks after injection of [18F]GEH121224 Life expectancy >3 months Diagnosis of locally advanced or metastatic breast cancer Target lesion diameter of ≥15 mm that has not been previously treated with radiotherapy Histologically confirmed locally advanced/metastatic breast cancer with a biopsy within the past 12 months confirming HER2-positive status by either IHC or FISH from primary tumor Previously received no more than 1 prior lines of systemic chemotherapy (including anti HER2 therapy) for metastatic breast cancer Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Adequate organ function as defined by: Hemoglobin ≥10 g/dL White blood cell count ≥3.0 × 109/L Platelet count ≥75 × 109/L Serum creatinine ≤1.4 mg/dL Aspartate aminotransferase and alanine aminotransferase ≤2× upper limit of normal (ULN) Total bilirubin ≤2× ULN or 3.0 mg/dL in patients with Gilbert's syndrome At least one lesion is fluorodeoxyglucose (FDG)-avid Exclusion Criteria: Patient has a primary non-breast malignancy (small dermatological malignancies such as basal cell carcinoma <10 mm are allowed) Pregnancy or breast-feeding or, for women of child-bearing potential, unwillingness to use an acceptable form of birth control Chronically active hepatitis B or C Current history of drug or alcohol abuse or any active liver disease Administration of other IMP within 30 days of screening Systemic therapy including anti-HER2 therapy within 2 weeks before enrollment Ongoing toxicity > grade 2 from previous standard or investigational therapies, according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 History of cardiac disease (myocardial infarction, arrhythmias requiring therapy, symptomatic valvular disease, cardiomyopathy, or pericarditis) Evidence of significant medical condition, ongoing severe disease, or laboratory finding that, in the opinion of the Investigator, makes it undesirable for the patient to participate in the study Severe claustrophobia, inability to lie flat or fit into the scanner (e.g., body weight ≥350 lbs [160 kg]), or any other inability to tolerate the PET scan Known allergies to any product used in this study or any constituents of GEH121224 (18F) Injection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Patients will be enrolled into 1 of 2 groups in a sequential manner. Group 1 will allow to study [18F]GEH121224 Biodistribution and Radiation Dosimetry. Group 2 will allow to study [18F]GEH121224 PET/CT Scan Test Retest.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [18F]GEH121224 - Group 1 - Biodistribution<br> | Drug: GEH121224 (18F) Injection<br>* Single GEH121224 (18F) Injection<br>Diagnostic Test: Dynamic and Static - PET/CT Scan<br>* Group 1: Dynamic whole-body PET/CT scan will start at the time of injection (8 sequential scans over 90 minutes anticipated) followed by static whole-body scans starting at 120 minutes and 240 minutes after injection.<br>|
| Experimental: [18F]GEH121224 - Group 2 - Reproducibility<br> | Drug: GEH121224 (18F) Injection<br>* Single GEH121224 (18F) Injection<br>Diagnostic Test: Static - PET/CT Scan<br>* Group 2: Static whole-body scans<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specific absorbed dose to the target lesions, specific absorbed dose per organ, and total effective dose of [18F]GEH121224. |  | 6 months | 
| Change in injection site status following administration of [18F]GEH121224 | The occurrence of post-administration injection site status outside the normal limits will be summarized. | Before [18F]GEH121224 administration, immediately after dynamic whole body PET/CT scan and single whole body scans | 
| Occurrence of Adverse Events (AEs) following administration of [18F]GEH121224 | An overall summary of AEs, SAEs, and [18F]GEH121224-emergent AEs will be presented, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class and preferred term. | 6 months | 
| Changes in heart rate as beats per minute following administration of [18F]GEH121224 | The occurrence of post-administration heart rate values outside the normal limits will be summarized. | Baseline, before [18F]GEH121224 administration, immediately after dynamic whole body PET/CT scan and single whole body scans | 
| Changes in blood pressure in mmHg following administration of [18F]GEH121224 | The occurrence of post-administration blood pressure values outside the normal limits will be summarized. | Baseline, before [18F]GEH121224 administration, immediately after dynamic whole body PET/CT scan and single whole body scans | 
| Changes in temperature as degree C following administration of [18F]GEH121224 | The occurrence of post-administration body temperature values outside the normal limits will be summarized. | Baseline, before [18F]GEH121224 administration, immediately after dynamic whole body PET/CT scan and single whole body scans | 
| Changes in respiration rate as breaths per minute following administration of [18F]GEH121224 | The occurrence of post-administration respiration rate values outside the normal limits will be summarized. | Baseline, before [18F]GEH121224 administration, immediately after dynamic whole body PET/CT scan and single whole body scans | 
| Change from baseline in the results of 12-lead electrocardiograms (ECGs) following administration of [18F]GEH121224 | Descriptive statistics will be used to describe the observed values and change from baseline for ECG intervals (PR, QTc, QRS or RR). | Baseline, before [18F]GEH121224 administration, immediately after single whole body PET/CT scans | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution | Time-activity curves will be generated and integrated to obtain the cumulated activity in each region, and these values will be used to determine the internal radiation dosimetry using the Medical Internal Radiation Dose (MIRD) schema. | 6 months | 
| Reproducibility | Variation in the relative standardized uptake values (SUVs) calculated from test and retest [18F]GEH121224 PET images. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2 positive, Breast Oncology