MITRAS: Study of 68GaNOTA-Anti-MMR-VHH2 in Oncological Lesions and Cardiovascular Atherosclerosis and Syndrome With Abnormal Immune Activation.
Study Details
Study Description
Brief Summary
Phase II study to evaluate the clinical potential of 68GaNOTA-anti-MMR-VHH2 for in vivo imaging of Macrophage Mannose Receptor (MMR)-expressing Macrophages by means of Positron Emission Tomography (PET) in patients with oncological lesions in need of non-surgical therapy and patients with cardiovascular atherosclerosis and syndrome with abnormal immune activation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cancer, lymphoma, carotid plaque, patients suspected for hemophagocytic lymphohistiocytosis Cohort 1: Patients diagnosed with pathology-proven squamous cell carcinomas of the head and neck in need of a non-surgical therapy. Cohort 2: Patients diagnosed with any malignancy with a solid component in need of immune checkpoint inhibitor-type immunotherapy. Cohort 3: Patients diagnosed with carotid plaque, planned for standard-of-care carotid endarterectomy. Cohort 4: Patients with a biopsy-proven Hodgkin (HL) or non-Hodgkin lymphoma (NHL) eligible for systemic treatment, radiotherapy or a combination of both. Cohort 5: Patients suspected for hemophagocytic lymphohistiocytosis (HLH), planned for (SOC) bone marrow biopsy |
Drug: 68GaNOTA-Anti-MMR-VHH2
All subjects will receive at least one single intravenous injection of the IMP followed by a total body PET/CT prior to receiving standard-of-care therapy.
For patients in cohorts 1 and 2: an optional injection of the IMP during or after therapy can be administered if a patient is treated with non-surgical modalities.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Correlation of uptake of 68GaNOTA-Anti-MMR-VHH2 before start of treatment in HNSCC lesions with time to treatment failure after radiotherapy or systemic treatment including immune checkpoint inhibition. (cohort 1) [up to 5 years]
Uptake will be measured in cancer lesions on PET/CT 1. Treatment response will be evaluated by assessing time to treatment failure and by assessment of status of patients for treatment failure (Y/N) at 6 months and 12 months after start of treatment
- Correlation of uptake of 68GaNOTA-Anti-MMR-VHH2 before start of treatment in solid cancer lesions with time to treatment failure after systemic treatment with immune checkpoint inhibition, either or not combined with other systemic therapies. (cohort 2) [up to 5 years]
Uptake will be measured in cancer lesions on PET/CT 1. Treatment response will be evaluated by assessing time to treatment failure and by assessment of status of patients for treatment failure (Y/N) at 6 months and 12 months after start of treatment
- Correlation of uptake of 68GaNOTA-Anti-MMR-VHH2 in atherosclerotic carotid plaques before surgery with the immunohistological MMR-staining of the excised atherosclerotic carotid plaque. (cohort 3) [Resection of lesion up to 21 days after PET/CT]
PET/CT and immunohistochemistry will be assessed using a semi-quantitative scale.
- Correlation of uptake of 68GaNOTA-Anti-MMR-VHH2 before start of treatment in Hodgkin and non-Hodgkin lymphoma patients (cohort 4). [up to 5 years]
Uptake will be measured in lymphoma-related lesions on PET/CT 1
- Correlation of uptake of 68GaNOTA-Anti-MMR-VHH2 in central bone on PET/CT with the presence of hemophagocytosis in bone marrow samples, and the presence of clinical risk factors (cohort 5). [up to 5 years]
PET/CT, results of additional blood sample analysis and bone marrow aspirate or trephine biopsy will be assessed using a semi-quantitative scale.
Eligibility Criteria
Criteria
COHORT SPECIFIC INCLUSION CRITERIA:
-
COHORT 1:
-
Patients who have given informed consent
-
Patients at least 18 years old
-
Patients diagnosed with biopsy-proven squamous cell carcinomas of the head and neck, independent of tumour stage.
-
In order to be eligible, a new non-surgical therapeutic approach should be considered by the treating physician(s).
-
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
-
Patient is 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 patient is eligible for systemic treatment, radiotherapy or a combination of both.
-
COHORT 5:
-
Patients who have given informed consent
-
Patients at least 18 years old
-
Patient who are planned to undergo bone marrow biopsy with suspected HLH by presence of ≥ 3 clinical risk factors:
-
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
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 1
-
Patients planned for a surgical resection of the tumour.
-
Patients with recent (< 1 week) gastrointestinal disorders (CTCAE v5.0 grade 3 or
- with diarrhoea as major symptom.
-
COHORT 2
-
Patients with recent (< 1 week) gastrointestinal disorders (CTCAE v5.0 grade 3 or
- with diarrhoea as major symptom.
- Patients diagnosed with squamous cell carcinomas of the head and neck. These patients can be included into Cohort I.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Uz Brussel | Brussels | Brussel | Belgium | 1090 |
Sponsors and Collaborators
- Universitair Ziekenhuis Brussel
Investigators
- Principal Investigator: Marleen Keyaerts, MD, Universitair Ziekenhuis Brussel
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UZBRU_VHH2_2
- 2020-002483-31