Imaging of specific immune cells in cancer and cardiovascular conditions

Phase II Study to Evaluate the Clinical Potential of 68GaNOTA-Anti-MMR-VHH2 for in Vivo Imaging of MMR-expressing Macrophages by Means of Positron Emission Tomography (PET) in Oncological Lesions,Cardiovascular Atherosclerosis,Syndrome With Abnormal Immune Activation and sarcoïdosis

This study is testing a new imaging method to see if it can help spot certain immune cells in people with cancer or heart conditions.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Universitair Ziekenhuis Brussel (other)
• Locations: 1 site (Brussels, Brussel)
• Trial ID: NCT04758650 on ClinicalTrials.gov

What this trial studies

This Phase II study evaluates the use of 68GaNOTA-anti-MMR-VHH2 for in vivo imaging of macrophages expressing the Macrophage Mannose Receptor (MMR) using Positron Emission Tomography (PET). The study focuses on patients with oncological lesions requiring non-surgical therapy, as well as those with cardiovascular atherosclerosis, abnormal immune activation syndromes, and sarcoidosis. Participants will be assessed based on specific inclusion criteria related to their conditions and tumor characteristics.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with biopsy-proven solid malignancies in the head and neck or those with cardiovascular atherosclerosis.

Not a fit: Patients with conditions not related to the specified malignancies or cardiovascular issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance the ability to non-invasively visualize and assess immune cell activity in various diseases, potentially leading to improved treatment strategies.

How similar studies have performed: Other studies utilizing PET imaging for similar purposes have shown promise, indicating potential for success in this approach.

Eligibility criteria

COHORT SPECIFIC INCLUSION CRITERIA:

* COHORT 1:

  - Patients who have given informed consent

  - Patients at least 18 years old

  - Patients with : A) biopsy-proven solid malignancy located in the head and neck, independent of tumour stage or pathological subtype, or B) suspected malignancy in the head and neck, planned for biopsy
  * In order to minimize partial volume effect, the diameter of at least 1 tumour lesion should be ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions.
  * Patients who already participated in the trial and who are diagnosed with progressive or recurrent disease can be re-included if all inclusion criteria and none of the exclusion criteria apply.
* COHORT 2:

  * Patients who have given informed consent
  * Patients at least 18 years old
  * Patient with a biopsy proven local, locally advanced or metastatic malignancy with a solid component that is at least ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions.
  * The patient is planned for immune checkpoint inhibition treatment, either or not combined with other systemic therapies.
  * Patients who already participated in the trial and who are diagnosed with progressive or recurrent disease can be re-included if all inclusion criteria and none of the exclusion criteria apply
* COHORT 3:

  * Patients who have given informed consent
  * Patients at least 18 years old
  * Patients planned for the surgical removal of an atherosclerotic plaque of the carotid artery, consisting of endarterectomy.
* COHORT 4:

  * Patients who have given informed consent
  * Patients at least 18 years old
  * Patient with a biopsy-proven Hodgkin or non-Hodgkin lymphoma
  * At time of inclusion, the patient presents with at least 1 lymphoma lesion of which the diameter should be ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions.
  * Diagnostic tissue sample is available for immunohistochemistry analysis, that was obtained \< 3 months prior to patient inclusion.
  * 18F-FDG-PET/CT has been performed \< 3 months prior to patient inclusion
  * The patients are eligible for systemic treatment, radiotherapy or a combination of both.
* COHORT 5:

  * Patients who have given informed consent
  * Patients at least 18 years old
  * Patients with suspicion of HLH, based on either a previous bone marrow sample showing hemofagocytis or based on the presence of at least 3 risk criteria as follows :
  * Fever ≥ 38,5°C
  * Splenomegaly
  * Bicytopenia, with at least 2 of the 3 following parameters:
  * Hb \< 9 g/dl and/or
  * Platelets \< 100 000/ml and/or
  * Neutrophils \< 1000/ml
  * Hypertriglyceridemia (fasting \> 265 mg/dl)µ
  * Ferritin \> 500 ng/ml
* COHORT 6:

  * Patients who have given informed consent
  * Patients at least 18 years old
  * Patients with :

A) Endomyocardial biopsy-proven cardiac sarcoidosis (CS) or B) suspected cardiac sarcoidosis based on the 2014 Hearth Rythm Society Expert Consensus Statement on the Diagnosis and Management of Arrhytmias Associated with Cardiac Sarcoidosis. At least one of the following criteria should be met :

* Steroid +/- Immunosuppressant responsive cardiomyopathy or heart block
* Unexplained reduced left ventricular ejection fraction (LVEF) \<40%
* Unexplained sustained (spontaneous or induced) ventricular tachycardia (VT)
* Mobitz type II 2nd-degree heart block or 3rd-degree heart block
* Patchy uptake on dedicated cardiac PET (in a pattern consistent with CS)
* Late Gadolinium Enhancement on Cardiovascular Magnetic Resonance (in a pattern consistent with CS)
* Positive gallium uptake (in a pattern consistent with CS)
* Histological Diagnosis from Myocardial Tissue
* Patients already included in cohort 7 with progression to cardiac sarcoidosis

  \*COHORT 7:
* Patients who have given informed consent
* Patients at least 18 years old
* Patients with biopsy-proven sarcoidosis

GENERAL EXCLUSION CRITERIA:

* Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher.
* Pregnant patients.
* Breast feeding patients.
* 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.
* When a patient exhibits symptoms correlated with SARS-CoV-2, the patient should be tested using the standard of care testing protocol, prior to inclusion. When the test results indicate an active SARS-CoV-2-infection, the patient is excluded for this trial.

COHORT SPECIFIC EXCLUSION CRITERIA

* COHORT 2

  * Patients with a biopsy-proven Hodgkin or non-Hodgkin lymphoma
  * Patients diagnosed with any malignancy of the head and neck. These patients can be included into Cohort I.
* COHORT 7 - Patients eligible for cohort 6

Where this trial is running

Brussels, Brussel

• Uz Brussel — Brussels, Brussel, Belgium (RECRUITING)

Study contacts

• Principal investigator: Tony Lahoutte, MD — Universitair Ziekenhuis Brussel
• Study coordinator: UZ Brussel

Conditions: Solid Malignancy Located in the Head and Neck, Cancer, Carotid Stenosis, Atherosclerosis of Artery, Hodgkin Lymphoma, Adult, Non Hodgkin Lymphoma, HLH, Cardiac Sarcoidosis