PET/CT with zirconium‑labelled girentuximab to image CAIX in liver and gastro‑entero‑pancreatic neuroendocrine tumors

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.

This will test whether a PET/CT scan using zirconium‑labelled girentuximab can find CAIX‑expressing hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and gastro‑entero‑pancreatic neuroendocrine tumors in adults.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Nantes University Hospital (Academic / other)
• Drugs / interventions: Chemotherapy, immunotherapy, radiation, girentuximab
• Locations: 2 sites (Nantes and 1 other locations)
• Trial ID: NCT06735560 on ClinicalTrials.gov

What this trial studies

The trial uses 89Zr‑labelled girentuximab as an immunoPET tracer targeting carbonic anhydrase IX (CAIX) to image HCC, ICC and selected GEP‑NEN patients. Eligible adults with at least one RECIST‑measurable lesion and ECOG 0–2 will receive a PET/CT with the tracer to determine tumor uptake and distribution. The design includes baskets for HCC/ICC and for progressive or specific GEP‑NEN subgroups to capture heterogeneous expression patterns. Imaging findings could inform lesion detection, staging, and potential selection for future CAIX‑targeted theranostic approaches.

Who should consider this trial

Good fit: Adults (≥18) with histologically proven HCC or ICC (newly diagnosed or recurrent/refractory) or with progressive GEP‑NENs meeting the protocol's criteria who have at least one RECIST‑evaluable lesion and ECOG performance status 0–2 are ideal candidates.

Not a fit: Patients with known hypersensitivity to zirconium‑89 or radiographic contrast agents, those who have recent or conflicting cancer treatments or other contraindications to PET/CT, and patients whose tumors do not express CAIX are unlikely to benefit.

Why it matters

Potential benefit: If successful, the tracer could help doctors detect and localize CAIX‑expressing liver and neuroendocrine tumors more accurately and may guide personalized treatment decisions or future targeted therapies.

How similar studies have performed: Radiolabelled girentuximab has shown promise as a PET tracer and as a theranostic partner in clear cell renal cell carcinoma, but its application in HCC, ICC and GEP‑NENs is novel and not yet established.

Eligibility criteria

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.

Where this trial is running

Nantes and 1 other locations

• CHU de Nantes — Nantes, France (Recruiting)
• AP-HP - Site de Beaujon — Paris, France (Not_yet_recruiting)

Study contacts

• Study coordinator: Clément BAILLY

Conditions Hepatocellular Carcinoma; Intrahepatic Cholangiocarcinoma; Neuroendocrine Tumors; immunoPET; CAIX; GEP-NEN; ICC; HCC