Repeatability of 68-GaNOTA-Anti-HER2 VHH1 PET/CT in Breast Carcinoma Patients

Study Overview
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Brief Summary
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Study objective: Cohort 1: To quantify the uptake of 68GaNOTA-Anti-HER2 VHH1 in local or distant metastases from breast carcinoma patients and to assess repeatability of the image-based HER2 quantification. The uptake will be correlated to results obtained via biopsy of the same lesion, if available. Cohort 2: To report on uptake of 68GaNOTA-Anti-HER2 VHH1 in different cancer types that might overexpress HER2 Cohort 3: To explore the feasibility and added value of 68GaNOTA-Anti-HER2 VHH1 in the neoadjuvant setting of HER2-expressing breast carcinoma Time schedule: After inclusion, patients will be injected intravenously with 37 - 185 MBq 68GaNOTA-Anti-HER2 VHH1 with a total mass of up to 200 μg NOTA-Anti-HER2 VHH1. Serum and plasma samples will be collected at injection. At 90 min after injection, a total body PET/CT scan will be performed. Patients in cohort 1 will undergo a second PET/CT procedure, identical to the first procedure, within 8 days, with a minimal interval of 18h and maximal interval of 8 days. Patients in cohort 2 can undergo an optional 18F-FDG-PET/CT within 21 days prior to or after 68GaNOTA-Anti-HER2 VHH1. In cohort 1 and 2, based on PET/CT images, up to 2 lesions will be selected for optional image-guided biopsy. Biopsy will be performed max. 28 days after the last PET/CT. Plasma and serum samples will be obtained between 60 and 365 days after first injection for patients in cohort 1 and between 42 and 365 days after first injection for patients in cohort 2. Patients in cohort 3 will undergo 68GaNOTA-Anti-HER2 VHH1 PET/CT prior to the start of neoadjuvant treatment and again after the last cycle of neoadjuvant treatment but prior to surgery. Plasma and serum samples will be obtained before each injection and between 42 and 365 days after the last injection.

Official Title
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Quantification of 68-GaNOTA-Anti-HER2 VHH1 Uptake in Metastasis of Breast Carcinoma Patients and Assessment of Repeatability (VUBAR) - Pilot Study

Conditions
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Metastatic Breast Carcinoma, Locally Advanced Breast Cancer, Cancer of Pancreas, Solid Tumor With Intermediate or High HER2 Expression, Salivary Gland Cancer, Gastric Cancer, Endometrial Cancer, Uterine Cancer, Non Small Cell Lung Cancer, Biliary Tract Cancer, Cholangiocarcinoma, Colorectal Cancer, Urothelial Carcinoma, Prostate Cancer

Intervention / Treatment
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* Drug: 68GaNOTA-Anti-HER2 VHH1


Participation Criteria
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Eligibility Criteria
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COHORT SPECIFIC INCLUSION CRITERIA: COHORT 1: Patients will only be included in the study if they meet all of the following criteria: Patient who has given informed consent Patient with age 18 years or older Patient with locally or distantly advanced breast carcinoma, with at least 1 lesion of at least 12 mm maximal diameter. For lymph node metastases, the largest diameter should be at least 15 mm and the short axis at least 12 mm. COHORT 2: Patients will only be included in the study if they meet all of the following criteria: Patient who has given informed consent Patient with age 18 years or older Patients with locally advanced, unresectable, or metastatic cancer disease , with at least 1 lesion of at least 10 mm maximal diameter (For lymph node metastases, short axis at least 10 mm) of any of the following types: breast carcinoma with low, intermediate or high HER2-expression, based on IHC 1+ or IHC 2+ or IHC 3+, as determined by local assessment on any of the available cancer tissues salivary gland cancer adenocarcinoma of the gastric body or gastro-esophageal junction endometrial cancer cancer of cervix uteri Non-small cell lung cancer biliary tract cancer including intra- or extrahepatic cholangiocarcinoma and tumors arising in the ampulla of Vater or gallbladder. pancreatic cancer colorectal cancer urothelial carcinoma, including transitional cell or predominantly transitional cell carcinoma of the renal pelvis, ureter, urinary bladder or urethra. prostate cancer Other solid malignant tumors with intermediate or high HER2-expression, based on IHC 2+ or IHC 3+, as determined by local assessment on any of the available cancer tissues Patients who have progressed following at least one prior systemic treatment for metastatic or advanced disease, or who have no satisfactory alternative treatment option, according to the treating physician (based on all available data such as medical imaging, lab results, clinical examination, …), and who are considered for a next line of systemic treatment. Patients who already participated in the trial and who are diagnosed with progressive or recurrent disease can be re-included if all inclusion criteria and none of the exclusion criteria apply. COHORT 3: Patients will only be included in the study if they meet all of the following criteria: Patient who has given informed consent Patient with age 18 years or older Patient with local or locally advanced HER2-positive (either IHC 3+ and/or ISH positive) breast carcinoma, who is planned for neo-adjuvant treatment prior to surgery, and who is suspected for axillary lymph node invasion, based on clinical assessment, ultrasound, CT or MRI, or who has a confirmed lymph node invasion Patients who either had 18F-FDG- PET/CT in the last 4 weeks before inclusion, or for whom 18F-FDG- PET/CT is planned before start of neoadjuvant treatment. GENERAL EXCLUSION CRITERIA: Patients will not be included in the study if one or more of the following criteria applies: Patient is pregnant Patient is breast feeding Patient with recent (< 1 week) gastrointestinal disorders with diarrhea as major symptom Patient with any serious active infection Patient who has any other life-threatening illness or organ system dysfunction, which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the test radiopharmaceutical Patient who cannot communicate reliably with the investigator Patient who is unlikely to cooperate with the requirements of the study Patient who is unwilling and/or unable to give informed consent Patient at increased risk of death from a pre-existing concurrent illness COHORT SPECIFIC EXCLUSION CRITERIA COHORT 1 & 3: Patient who participated already in this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Interventional Model Description: The trial consists of 3 different patient cohorts that are each investigated using a new diagnostic imaging radiopharmaceutical
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cancer patients<br>Cohort 1: locally advanced or metastatic breast cancer patients Cohort 2: Patients with locally advanced, unresectable, or metastatic cancer disease of breast with low, intermediate or high HER2-expression, salivary gland; gastric body or gastro-esophageal junction; endometrium; uterus; lung; biliary tract; gallbladder; pacreas; colorectum; urothelium; prostate; other solid with intermediate or high HER2-expression Cohort 3: Patients with local or locally advanced HER2-+ breast carcinoma, who are planned for neo-adjuvant treatment prior to surgery, and who are suspected for axillary lymph node invasion. | Drug: 68GaNOTA-Anti-HER2 VHH1<br>* All subjects will receive at least one single intravenous injection of the IMP followed by a total body PET/CT prior to receiving standard-of-care therapy. A second injection of the IMP can be administered before or during standard-of-care treatment, depending on cohort.<br>* Other names: HER2-PET/CT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repeatability of lesional PET/CT characteristics | The lesional tracer uptake in local and distant metastases of at least 12 mm (for lymph nodes short axis) will be measured on both PET/CT's (expressed as standard uptake value (SUV) and repeatability will be calculated. | 90 min post injection | 
| Tracer update of 68GaNOTA-Anti-HER2 VHH1 in different cancer types | The lesional tracer uptake in different cancer types of at least 10 mm maximal diameter (for lymph nodes short axis) will be measured on PET/CT (expressed as standard uptake value (SUV). | 90 min post injection | 
| Feasibility and added value of 68GaNOTA-Anti-HER2 in neoadjuvant setting of breast carcinoma |  | time of surgery following neo-adjuvant treatment (typically within 14 days following the second intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within-patient tumor heterogeneity for HER2 expression using PET/CT imaging | Within-patient tumor heterogeneity for HER2 expression, observed on 68GaNOTA-Anti-HER2 VHH1 PET/CT or biopsy analyses | 90 min post injection | 
| Immunogenicity | Immunogenicity assessed on plasma samples obtained prior to injection of the IMP and obtained between 60 and 365 days after the (first) injection | prior to and between 60 and 365 days after the first injection | 
| Histopathological results of biopsied lesions and correlation with PET/CT results | semi-quantitative score of HER2 expression using immunohistochemistry performed on biopsied/resected tissues if available | max 28 days after the second PET/CT | 
| Influence image-guide biopsy on patient management | To determine in which relative number of patients, the patient management was altered after 68GaNOTA-Anti-HER2 VHH1 PET/CT and the subsequent optional biopsy | Within 3 months following the last intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2