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

Phase 1

Completed

• Conditions: Malignant Solid Tumor; Melanoma (Skin); Breast Cancer
• Interventions: Drug: 68GaNOTA-Anti-MMR-VHH2

• Registration Number: NCT04168528
• Lead Sponsor: Universitair Ziekenhuis Brussel

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-11-05
• Study First Submitted: 2019-11-07
• Study First Submitted QC: 2019-11-15
• Study First Posted: 2019-11-19
• Status Verified: 2024-12
• Primary Completion: 2024-12-04
• Study Completion: 2024-12-04
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part I: safety, tolerability, biodistribution and dosimetry	68GaNOTA-Anti-MMR-VHH2	Phase I
Part II: tumor targeting potential and correlation to IHC	68GaNOTA-Anti-MMR-VHH2	Phase II

Primary Outcome Measures

Name	Time	Method
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).	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).	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).	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).	Resection of lesion up to 14 days after PET/CT	PET/CT and immunohistochemistry will be assessed using a semi-quantitative scale.

Trial Locations

Locations (1)

Uz Brussel; 🇧🇪 Brussels, Belgium