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Precision medicine represents a major goal in oncology. It has its underpinning in the identification of biomarkers with diagnostic, prognostic, or predictive values. Gastro-entero-pancreatic neuroendocrine neoplasia (GEP-NENs) are rare tumors, but their frequency is increasing. In this context, the tumor expression of carbonic anhydrase IX (CAIX), complemented by a restricted profile in normal tissues, provides an opportunity for therapeutic targeting and precision medicine. Indeed, radiolabeling the anti-CAIX monoclonal antibody girentuximab with Zirconium 89 has shown promise as a novel positron emission tomography (PET) tracer and labeling with 177 Lutetium promise as a therapeutic agent in clear cell renal cell carcinoma (ccRCC) in the context of a theranostic approach. The purpose of this study is to evaluate the use of 89Zr-labeled girentuximab (89Zr-TLX250) as a novel, carbonic anhydrase IX (CAIX) targeted PET/CT tracer for the imaging of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms, Hepatocellular Carcinoma or IntraHepatic Cholangiocarcinoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 89Zr-TLX250 | Experimental | Patients will be injected with a single dose of 89Zr-TLX250. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 89Zr-TLX250 PET/CT | Radiation | Patients will receive 89Zr-TLX250 for detection of CAIX-expressing tumor by PET imaging. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Tumor targeting of 89Zr-TLX250 PET | Number of tumor lesions detected by 89Zr-TLX250 PET in comparison with the lesions identified by morphological imaging at baseline. | Day 5 |
| Tumor targeting of 89Zr-TLX250 PET | Location of tumor lesions detected by 89Zr-TLX250 PET in comparison with the lesions identified by morphological imaging at baseline. | Day 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of tolerability | Unexpected immediate adverse events up to post-administration of 89Zr-TLX250. | Hour 2 |
| Evaluation of tolerability | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
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Inclusion Criteria:
Provided written informed consent.
Patients aged ≥ 18 years.
- For basket 1 and 2: HCC or ICC histologically proven: newly diagnosed patients or patients with suspected refractory, residual, or recurrent disease.
- For basket 3: Progressive GEP-NENs with low or heterogeneous expression of SSTR2 or progressive pancreatic NENs which previously received at least two systemic treatments (excluding SSA) or pancreatic NENs with germline or somatic VHL mutation or G3 GEP-NENs .
Presence of at least one morphological evaluable lesion according to RECIST 1.1 using contrast CT/MRI.
Patients must have an ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 2.
For cirrhotic patients: Child-Pugh ≤ B7.
Patient affiliated to or beneficiary of the National Health Service.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clément BAILLY | Contact | +33240084136 | clement.bailly@chu-nantes.fr | |
| Astrid GARREAU | Contact | +33253482840 | astrid.garreau@chu-nantes.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Nantes | Recruiting | Nantes | France |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D018281 | Cholangiocarcinoma |
| C562580 | Cirrhosis, Familial, with Pulmonary Hypertension |
| D018358 | Neuroendocrine Tumors |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| Day 8 |
| Diagnostic efficacy | Sensitivity of 89Zr-TLX250 PET/CT in the detection of tumor lesions as compared to a composite truth standard (determined on the basis of histology and conventional morphological or PET imaging). | Month 3 |
| Diagnostic efficacy | Concordance of 89Zr-TLX250 PET/CT in the detection of tumor lesions as compared to a composite truth standard (determined on the basis of histology and conventional morphological or PET imaging). | Month 3 |
| Assessment of tumor uptake | Tumor quantitative measures on 89Zr-TLX250 PET. | Day 8 |
| Correlation with CAIX | Assessment of the correlation between the normalized uptake values (SUVmax) of 89Zr-TLX250 positive lesions and CAIX histological expression will be done by comparing the 89Zr-TLX250 semi-quantitative data with the immunohistochemical results (IHC) of biopsied lesions. | Day 8 |
| Assessment of the absorbed doses | Quantitative biodistribution of 89Zr-TLX250 will be evaluated from sequential whole body PET-CT imaging and pharmacokinetic data. | Day 0 |
| Assessment of the absorbed doses | Quantitative biodistribution of 89Zr-TLX250 will be evaluated from sequential whole body PET-CT imaging and pharmacokinetic data. | Day 1 |
| Assessment of the absorbed doses | Quantitative biodistribution of 89Zr-TLX250 will be evaluated from sequential whole body PET-CT imaging and pharmacokinetic data. | Day 5 |
| Assessment of the absorbed doses | Quantitative biodistribution of 89Zr-TLX250 will be evaluated from sequential whole body PET-CT imaging and pharmacokinetic data. | Day 7 |
| AP-HP - Site de Beaujon | Not yet recruiting | Paris | France |
|
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009380 | Neoplasms, Nerve Tissue |