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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 13
- Locations
- 2
- Primary Endpoint
- 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).
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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
- •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
Arms & Interventions
Part I: safety, tolerability, biodistribution and dosimetry
Phase I
Intervention: 68GaNOTA-Anti-MMR-VHH2 (Drug)
Part II: tumor targeting potential and correlation to IHC
Phase II
Intervention: 68GaNOTA-Anti-MMR-VHH2 (Drug)
Outcomes
Primary Outcomes
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).
Time Frame: Immediately after injection up to 3 hrs after injection
Measured in standard uptake values in PET/CT imaging and expressed in relation to the injected activity.
Tolerability and safety of 68GaNOTA-Anti-MMR-VHH2: reported as type, frequency and severity (graded according to the CTCAEv5) (Part I).
Time Frame: Before injection up until 6 hrs after injection
Assessed using physical examination and blood sampling for hematology and clinical chemistry.
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).
Time Frame: 10 min up to 3 hrs after injection
Dosimetry will be calculated using the OLINDA software.
Tumor targeting potential using PET/CT and correlation to immunohistological MMR staining after resection: assessed using correlation coefficient (Part II).
Time Frame: Resection of lesion up to 14 days after PET/CT
PET/CT and immunohistochemistry will be assessed using a semi-quantitative scale.
Secondary Outcomes
No secondary outcomes reported