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

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

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 Overview

• Status: Recruiting
• Conditions: Breast Cancer; Melanoma (Skin); Malignant Solid Tumor
• Intervention / Treatment: Drug: 68GaNOTA-Anti-MMR-VHH2

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: UZ BRUSSEL; Phone Number: +3224776013; Email: nucgmail@uzbrussel.be

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Recruiting
    • UZ Brussel
    • Contact: MD
    • Contact: UZ BRUSSEL; Phone Number: +3224776013; Email: nucgmail@uzbrussel.be
    • Principal Investigator: Tony Lahoutte, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Collaborators: Kom Op Tegen Kanker
• Investigators: Principal Investigator: Tony Lahoutte, MD, Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PET/CT; MMR-PET/CT; Macrophage PET/CT
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: UZBRU_VHH2_1; 2017-001471-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No