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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04168528
• Other study ID #: UZBRU_VHH2_1
• Secondary ID: 2017-001471-23
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 5, 2019
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Universitair Ziekenhuis Brussel
• Contact: UZ Brussel
• Phone: +3224776013
• Email: nucgmail[@]uzbrussel.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: December 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Malignant Solid Tumor
• Melanoma
• Melanoma (Skin)

Intervention

Drug:
• 68GaNOTA-Anti-MMR-VHH2
Injection of the radiopharmaceutical and PET/CT imaging

Locations

Country	Name	City	State
Belgium	Uz Brussel	Brussels

Sponsors (2)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel	Kom Op Tegen Kanker

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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