E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
C1: malignancies of the head and neck. C2: malignancy with a solid component C3: carotid plaque, planned for (SOC) carotid endarterectomy. C4: biopsy-proven Hodgkin or non-Hodgkin lymphoma. C5: suspected for hemophagocytic lymphohistiocytosis (HLH), planned for (SOC) bone marrow biopsy in case it is not done before. C6: biopsy proven or suspected endomyocardial sarcoidosis C7: biopsy proven sarcoidosis |
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E.1.1.1 | Medical condition in easily understood language |
Head-and-Neck cancer, cancer with solid lesions, atherosclerosis of large artery in the neck, Hodgkin/non-Hogdkin Lymphoma, hemophagocytic lymphohistiocytosis, cardiac sarcoidosis and sarcoidosis. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
(1) To correlate uptake of 68GaNOTA-Anti-MMR-VHH2 of the selected lesion(s) with the therapeutic tumour response (cohorts 1 and 2) (2) To correlate uptake of 68GaNOTA-Anti-MMR-VHH2 with the expression of MMR using immunohistochemistry (cohorts 1, 3 and 6 if tissue is available) (3) To evaluate uptake of 68GaNOTA-Anti-MMR-VHH2 in the selected lesion(s) (cohort 4, 6 and 7) (4) To correlate uptake of 68GaNOTA-Anti-MMR-VHH2 in central bone with the presence of hemophagocytosis in bone marrow samples, and the presence of clinical risk factors for hemophagocytic lymphohistiocytosis (HLH) (cohort 5).
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E.2.2 | Secondary objectives of the trial |
Determine proportion of subject with malignancies of HN that show uptake on PET/CT (C1). Assess the difference in uptake before and during or after treatment. Correlate this difference in uptake to time to treatment failure (C1 and 2 (except radiotherapy). To characterize heterogeneity of uptake in patients with solid cancer lesions before and during or treatment (C2). To correlate the uptake of 68GaNOTA-Anti-MMR-VHH2 in lymphoma-related lesions with the immunohistological MMR-staining on available lymphoma tissue before treatment (C4) To correlate the uptake of 68GaNOTA-Anti-MMR-VHH2 in lymphoma-related lesions with serum MMR (sMMR) level at diagnosis (base-line) (C4) To evaluate sMMR levels before, during and after treatment (C4) To correlate serum MMR with the presence of hemophagocytosis in bone marrow samples (C5) To correlate the uptake of 68GaNOTA-Anti-MMR-VHH2 in sarcoidosis-related lesions with the the presence of M2-macrophages, if biopsy was performed (C6, C7)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Cohort 1: Adult patients with a suspected or diagnosed malignancy of the head and neck ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions. Cohort 2: Adult patients diagnosed with any malignancy with an anatomic location other than the head and neck with a solid component ≥10mm, treated with immune checkpoint inhibition. Cohort 3: Adult patients planned for surgical removal of an atherosclerotic plaque of the carotid artery by means of endarterectomy. Cohort 4: Adult patients diagnosed with Hodgkin or non-Hodgkin lymphoma 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. Cohort 5: Adult patients with suspicion of HLH, based on either a previous bone marrow sample showing hemofagocytosis or based on the presence of at least 3 risk criteria. Cohort 6: Adult patients with endomyocardial biopsy proven cardiac sarcoidosis or suspected CS according to the Heart Rhythm Society (HRS) consensus recommendation. Cohort 7: Adult patients with biopsy-proven sarcoidosis
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E.4 | Principal exclusion criteria |
- Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher. - Pregnant patients - Breast feeding patients - Patients with any serious active infection (cohort 1,2,3) - 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Cohort 1: - Uptake in cancer lesions on PET/CT 1 - Time to treatment failure - Status of patients for treatment failure at 6 months and 12 months after start of treatment (Y/N)
Cohort 2: - Uptake in cancer lesions on PET/CT 1 - Time to treatment failure - Status of patients for treatment failure at 6 months and 12 months after start of treatment (Y/N)
Cohort 3: - Uptake in excised atherosclerotic plaque on PET/CT 1 - Immunohistological MMR staining of excised atherosclerotic plaque, scored visually by interpreter
Cohort 4: - Tracer uptake in lymphoma-related lesions on MMR-PET/CT 1
Cohort 5: - Tracer uptake in bone marrow on MMR-PET/CT 1 - Bone marrow aspirate or trephine biopsy, scored visually by interpreter - Results of additional blood sample analysis to determine clinical risk factor
Cohort 6: - Uptake in lesions with known cardiac sarcoidosis on MMR-PET/CT on PET/CT 1, if biopsy was performed
Cohort 7: - Uptake in lesions involved with sarcoidosis on MMR-PET/CT
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluations will be done in batch analysis. |
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E.5.2 | Secondary end point(s) |
Cohort 1: - Uptake in contralateral normal tissue on PET/CT 1 - Uptake in cancer in lesions on PET/CT 2
Cohort 2: - Uptake in contralateral normal tissue on PET/CT 1 - Uptake in cancer in lesions on PET/CT 2 - Uptake in different areas of a cancer lesions of at least 20 mm on PET/CT 1 and PET/CT 2
Cohort 3: - Uptake in non-excised atherosclerotic plaques on PET/CT 1
Cohort 4: - Uptake in lymphoma-related lesions on MMR-PET/CT 1 - Immunohistological MMR staining of excised lymphoma tissue, scored visually by interpreter using a semi-quantitative scoring method - sMMR presence at baseline, at interim analysis, at end-of-treatment
Cohort 5: - Bone marrow aspirate or threphine biopsy, scored visually by interpreter - sMMR presence
Cohort 6: - Immunohistochemistry for CD68 (macrophages) and CD206 (M2) on biopsies of the sarcoidosis related lesion(s). - Uptake in sarcoidosis-related lesions on MMR-PET/CT on PET/CT 1
Cohort 7: - Immunohistochemistry for CD68 (macrophages) and CD206 (M2) on biopsies of the sarcoidosis related lesion(s). - Uptake in sarcoidosis related lesions on MMR-PET/CT - Difference in uptake in sarcoidosis related lesions on MMR-PET/CT 1 and 2 - Treatment response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluations will be done in batch analysis. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |