Hepatocellular Carcinoma (HCC), Intrahepatic Cholangiocarcinoma (Icc), Neuroendocrine Tumors
Conditions
Keywords
immunoPET, CAIX, GEP-NEN, ICC, HCC
Brief summary
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.
Interventions
RADIATION89Zr-TLX250 PET/CT
Patients will receive 89Zr-TLX250 for detection of CAIX-expressing tumor by PET imaging.
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provided written informed consent. 2. Patients aged ≥ 18 years. 3. \- 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 . 4. Presence of at least one morphological evaluable lesion according to RECIST 1.1 using contrast CT/MRI. 5. Patients must have an ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 2. 6. For cirrhotic patients: Child-Pugh ≤ B7. 7. Patient affiliated to or beneficiary of the National Health Service.
Exclusion criteria
1. Known hypersensitivity to zirconium-89, to any excipient or derivative or to radiographic contrast agents. 2. Chemotherapy, extensive external beam radiation, immunotherapy, targeted therapy, or angiogenesis inhibitors within 2 weeks prior to 89Zr-TLX250 administration. 3. Radionucleide targeted therapy prior to inclusion within 3 months prior to inclusion. 4. Radioembolization within 3 months prior to inclusion. 5. Uncontrolled brain or spinal cord metastasis. 6. Cardiac disease with New York Heart Association classification of III or IV. 7. Life expectancy shorter than 4 months. 8. Any major surgery within 4 weeks before enrollment. 9. Any uncontrolled significant medical, psychiatric or surgical condition (active infection (subjects with known human immunodeficiency virus (HIV) positive)), unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension, poorly controlled diabetes mellitus (glycated haemoglobin (HbA1c) ≥9%), uncontrolled congestive heart disease, etc.) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject's safety or that would limit compliance with the objectives and assessments of the study. 10. Other known malignancies (except for fully-resected non-melanoma skin cancer or cervical cancer in situ) unless definitively treated and proven no evidence of recurrence for 2 years. 11. Women who are pregnant or breastfeeding. A serum pregnancy test will be performed at the start of the study for all female subjects of childbearing potential. 12. Patient under guardianship or trusteeship. 13. Patient under judicial protection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor targeting of 89Zr-TLX250 PET | Day 5 | Number of tumor lesions detected by 89Zr-TLX250 PET in comparison with the lesions identified by morphological imaging at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of tolerability | Hour 2 | Unexpected immediate adverse events up to post-administration of 89Zr-TLX250. |
| Diagnostic efficacy | Month 3 | 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). |
| Assessment of tumor uptake | Day 8 | Tumor quantitative measures on 89Zr-TLX250 PET. |
| Correlation with CAIX | Day 8 | 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. |
| Assessment of the absorbed doses | Day 0 | Quantitative biodistribution of 89Zr-TLX250 will be evaluated from sequential whole body PET-CT imaging and pharmacokinetic data. |
Countries
France
Contacts
CONTACTClément BAILLY
CONTACTAstrid GARREAU
Outcome results
None listed