Clinical trial NCT06735560: Study Assessing PET Imaging With Zirconium-labelled Girentuximab in Patients With HCC, ICC or NEN
Official title: Prospective Pilot Study Assessing Imaging Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) PET-CT in Patients With HepatoCellular Carcinoma, IntraHepatic CholangioCarcinoma or Gastro-Entero-Pancreatic Neuroendocrine Neoplasms
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma (HCC)
Intrahepatic Cholangiocarcinoma (Icc)
Neuroendocrine Tumors
Keywords: immunoPET
CAIX
GEP-NEN
ICC
HCC
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2024-12-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: Inclusion Criteria:

1. Provided written informed consent.
2. Patients aged ≥ 18 years.
3. Histologically confirmed, unresectable locally advanced or metastatic solid tumors of:

   * HCC or ICC: expressing CAIX (less than 2 years), not eligible for local or loco- regional treatment, after failure of first line systemic therapy. In addition, for ICC, after targeted therapy in case of IDH1 mutation or FGFR fusion.
   * Progressive GEP-NENs (2019 WHO classification), functioning or non-function- ing, without or with low SSTR2 expression, after at least one line of standard therapy.
4. Presence of at least one morphological evaluable lesion according to RECIST 1.1 using contrast CT/MRI.
5. Patients should not have received further antitumor therapy once disease progression is documented.
6. Patients must have an ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 2.
7. For cirrhotic patients: Child-Pugh A.
8. 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 4 weeks prior to inclusion.
3. Radionucleide targeted therapy prior to inclusion within 6 months prior to inclusion.
4. Radioembolization within 3 months prior to inclusion.
5. Uncontrolled brain or spinal cord metastasis. Patients with a history of brain metastases must have a head CT or MRI with contrast to document stable brain disease 3 months prior to inclusion in the study.
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 or refusing effective contraception method.
12. Patient under guardianship or trusteeship.
13. Patient under judicial protection.

Primary outcomes:
measure: Tumor targeting of 89Zr-TLX250 PET
timeFrame: Day 5
measure: Tumor targeting of 89Zr-TLX250 PET
timeFrame: Day 5
Secondary outcomes:
measure: Evaluation of tolerability
timeFrame: Hour 2
measure: Evaluation of tolerability
timeFrame: Day 8
measure: Diagnostic efficacy
timeFrame: Month 3
measure: Diagnostic efficacy
timeFrame: Month 3
measure: Assessment of tumor uptake
timeFrame: Day 8
measure: Correlation with CAIX
timeFrame: Day 8
measure: Assessment of the absorbed doses
timeFrame: Day 0
measure: Assessment of the absorbed doses
timeFrame: Day 1
measure: Assessment of the absorbed doses
timeFrame: Day 5
measure: Assessment of the absorbed doses
timeFrame: Day 7
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: AP-HP - Site de Beaujon
Study officials:
References: