Phase I/IIa Study of 68GaNOTA-Anti-MMR-VHH2 for PET/CT

Study Overview
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Brief Summary
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Phase I study to evaluate the human safety and tolerability, biodistribution and dosimetry of 68GaNOTA-Anti-MMR-VHH2 Phase IIa study to evaluate tumour uptake of 68Ga-NOTA-anti-MMR-VHH2 in patients with breast cancer or melanoma. To correlate uptake of 68Ga-NOTA-anti-MMR-VHH2 in cancer lesions to immunohistological MMR staining after resection or biopsy of the same lesion.

Official Title
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Phase I/IIa Study to Evaluate the Safety, Biodistribution, Radiation Dosimetry and Tumor Imaging Potential of 68GaNOTA-Anti-MMR-VHH2, a New Radiopharmaceutical for in Vivo Imaging of Tumour-Associated Macrophages by Means of PET : UZBRU_VHH2_1

Conditions
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Malignant Solid Tumor, Breast Cancer, Melanoma (Skin)

Intervention / Treatment
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* Drug: 68GaNOTA-Anti-MMR-VHH2


Participation Criteria
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Eligibility Criteria
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PART I: Inclusion Criteria: Patients will only be included in the study if they meet all of the following criteria: Patients who have given informed consent Patients at least 18 years old Patients with local, locally advanced or metastatic disease of a malignant solid tumor. In order to minimize partial volume effect the diameter of at least 1 tumor lesion should be ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions. Exclusion Criteria: Patients will not be included in the study if one of the following criteria applies: Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher Pregnant patients Breast feeding patients Patients with abnormal liver (Bilirubin ≥1.5 x ULN, ALT (SGPT) ≥3 x ULN) or kidney function (Serum creatinine clearance ≤50 ml/min as calculated with Cockcroft-Gault formula) Patients with recent (< 1 week) gastrointestinal disorders (CTCAE v4.0 grade 3 or 4) with diarrhea as major symptom Patients with any serious active infection Patients who have 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 safety of the test radiopharmaceutical Patients who cannot communicate reliably with the investigator Patients who are unlikely to cooperate with the requirements of the study Patients who are unwilling and/or unable to give informed consent Patients at increased risk of death from a pre-existing concurrent illness Patients who participated already in this study PART II: Inclusion Criteria: Patients will only be included in the study if they meet all of the following criteria: Patients who have given informed consent Patients at least 18 years old Patients diagnosed with a local, locally advanced or metastatic disease, with any of the following cancer types : Triple-negative breast carcinoma, Hormone-receptor negative (HR-), HER2+ breast carcinoma, with HER2-expression defined as HER2+ on ISH or 3+ on IHC, as determined by local assessment on any of the available cancer tissues Melanoma Patients who have had a biopsy of at least one lesion or who are planned to undergo standard-of-care resection or biopsy of at least one lesion, in order to minimize partial volume effect, the diameter of that lesion should be ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions. Exclusion Criteria: Patients will not be included in the study if one of the following criteria applies: Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher Pregnant patients Breast feeding patients Patients with recent (< 1 week) gastrointestinal disorders (CTCAE v4.0 grade 3 or 4) with diarrhea as major symptom Patients with any serious active infection Patients who have 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 safety of the test radiopharmaceutical Patients who cannot communicate reliably with the investigator Patients who are unlikely to cooperate with the requirements of the study Patients who are unwilling and/or unable to give informed consent Patients at increased risk of death from a pre-existing concurrent illness Patients 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I: safety, tolerability, biodistribution and dosimetry<br>Phase I | Drug: 68GaNOTA-Anti-MMR-VHH2<br>* Injection of the radiopharmaceutical and PET/CT imaging<br>|
| Experimental: Part II: tumor targeting potential and correlation to IHC<br>Phase II | Drug: 68GaNOTA-Anti-MMR-VHH2<br>* Injection of the radiopharmaceutical and PET/CT imaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability and safety of 68GaNOTA-Anti-MMR-VHH2: reported as type, frequency and severity (graded according to the CTCAEv5) (Part I). | Assessed using physical examination and blood sampling for hematology and clinical chemistry. | Before injection up until 6 hrs after injection | 
| Human biodistribution using blood sampling and PET/CT imaging: reported as relative uptake values per organ at 10, 90 and 150 minutes per individual subject and as a mean over all subjects (Part I). | Measured in standard uptake values in PET/CT imaging and expressed in relation to the injected activity. | Immediately after injection up to 3 hrs after injection | 
| Human dosimetry using PET/CT imaging data: radiation dose to individual organs and the equivalent dose for the whole body of each subject and as a mean over all subjects (Part I). | Dosimetry will be calculated using the OLINDA software. | 10 min up to 3 hrs after injection | 
| Tumor targeting potential using PET/CT and correlation to immunohistological MMR staining after resection: assessed using correlation coefficient (Part II). | PET/CT and immunohistochemistry will be assessed using a semi-quantitative scale. | Resection of lesion up to 14 days after PET/CT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET/CT, MMR-PET/CT, Macrophage PET/CT