Study Assessing PET Imaging With Zirconium-labelled Girentuximab in Patients With HCC, BTC or NEN (ELEGANCE)

Prospective Pilot Study Assessing Imaging Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) PET-CT in Patients With HepatoCellular Carcinoma, Biliary Tract Carcers or Gastro-Entero-Pancreatic Neuroendocrine Neoplasms.

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma (HCC); Neuroendocrine Tumors; Intrahepatic Cholangiocarcinoma (Icc)
• Intervention / Treatment: Radiation: 89Zr-TLX250 PET/CT

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Clément BAILLY; Phone Number: +33240084136; Email: clement.bailly@chu-nantes.fr
• Study Contact Backup: Name: Astrid GARREAU; Phone Number: +33253482840; Email: astrid.garreau@chu-nantes.fr

Study Locations

• France
  • Nantes, France
    • Recruiting
    • Chu de Nantes
    • Contact: Clément BAILLY; Phone Number: +33240084136; Email: clement.bailly@chu-nantes.fr
    • Contact: Yann TOUCHEFEU; Phone Number: +33240083152; Email: yann.touchefeu@chu-nantes.fr
  • Paris, France
    • Not yet recruiting
    • AP-HP - Site de Beaujon
    • Contact: Rachida LEBTAHI; Phone Number: +33140875169; Email: rachida.lebtahi@aphp.fr
    • Contact: Mohamed BOUATTOUR; Phone Number: +33140875614; Email: mohamed.bouattour@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 89Zr-TLX250; Patients will be injected with a single dose of 89Zr-TLX250.	Radiation: 89Zr-TLX250 PET/CT; Patients will receive 89Zr-TLX250 for detection of CAIX-expressing tumor by PET imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2025
• Primary Completion (Estimated): May 4, 2027
• Study Completion (Estimated): August 4, 2027

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HCC; ICC; CAIX; GEP-NEN; immunoPET
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Hepatocellular; Cholangiocarcinoma; Neuroendocrine Tumors; Cirrhosis, Familial, with Pulmonary Hypertension
• Other Study ID Numbers: RC23_0453

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No