Clinical trial NCT04168528: Phase I/IIa Study of 68GaNOTA-Anti-MMR-VHH2 for PET/CT
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malignant Solid Tumor
Breast Cancer
Melanoma (Skin)
Keywords: PET/CT
MMR-PET/CT
Macrophage PET/CT
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
Collaborators: name: Kom Op Tegen Kanker
First posted: 2019-11-19
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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

Primary outcomes:
measure: Tolerability and safety of 68GaNOTA-Anti-MMR-VHH2: reported as type, frequency and severity (graded according to the CTCAEv5) (Part I).
timeFrame: Before injection up until 6 hrs after injection
measure: 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).
timeFrame: Immediately after injection up to 3 hrs after injection
measure: 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).
timeFrame: 10 min up to 3 hrs after injection
measure: Tumor targeting potential using PET/CT and correlation to immunohistological MMR staining after resection: assessed using correlation coefficient (Part II).
timeFrame: Resection of lesion up to 14 days after PET/CT
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Uz Brussel
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Tony LAHOUTTE, MD
role: PRINCIPAL_INVESTIGATOR
References: