Intra-arterial Hepatic (IAH) Infusion of Radiolabelled Somatostatin Analogs in GEP-NET Patients With Dominant Liver Metastases

• Status: Not yet recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The management of liver metastases in neuroendocrine neoplasms is challenging. Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs (SSA) is one of the most promising therapeutic options. As liver is the most frequent site of metastatic disease, our project proposes to compare administration of radiolabeled SSA by arterial intrahepatic infusion (experimental approach) vs intravenous administration (conventional). Evaluation will be made by (i) comparing 68Ga-DOTA-peptides uptake after intra-hepatic versus intravenous route (imaging), (ii) by evaluating the safety of an additional intra-hepatic administration of therapeutic radiolabeled SSA (therapy).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Bordeaux
• Collaborator: Advanced Accelerator Applications
• Treatments: Lutetium Lu 177 dotatate

Criteria

Inclusion Criteria:

• Histologically proven well differentiated neuroendocrine tumor (NET) of gastrointestinal or pancreatic origin (GEP).

• Patients are progressive after treatment with cold somatostatin analog (within 12 months according to RECIST)

• Patient has received 4 standard of care LUTATHERA® cycles

• Liver Metastatic disease dominant or exclusive and assessable by RECIST 1.1, and not amenable to surgical resection after the last cycle

• ECOG performance status 0-2

• Adequate kidney and liver function: creatinine clearance ≥ 50 mL/min, ALT/AST ≤ 2,5x the upper limit of normal

• With no evidence of hematologic alteration after 4 LUTATHERA® cycles: hemoglobin ≥ 8 g/dL, neutrophils ≥ 1500/ mm3, platelets ≥ 100.000/mm3

• Age ≥ 18 years, no superior limit

• Contraception required in pre-menopausal female and men for at least 6 months after the last LUTATHERA ® injection.

• Patient´s signed written informed consent

• Patient affiliated to a social security system

Exclusion Criteria:

• Patients with complete response defined by the absence of lesion according to RECIST 1.1 realized during morphological imaging at inclusion (chest-abdomen-pelvis CT scan and hepatic MRI)

• No residual uptake according to standard 177-Lu scintigraphy performed in the clinical routine 24 hours after each LUTATHERA IV treatment

• Carcinoid heart disease (LVEF < 40%)

• Dominant or threatening extrahepatic metastases or that may affect vital prognosis

• Contraindications to intra-hepatic arterial infusion (coagulation disorders, portal thrombosis, intra-hepatic biliary tract dilatation, digestive or biliary anastomosis or fistula, cirrhosis (Child Pugh B8 or C…)

• Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.

• Heart failure, myocardial infarction, stroke, uncontrolled arterial hypertension under optimal treatment (≥ 160/95 mmHg), pulmonary embolism or revascularization procedure, unstable angina pectoris, uncontrolled cardiac arrhythmia, and clinically significant bradycardia during the last 12 months.

• Individuals under legal protection or unable of giving their informed consent

• Pregnancy or breast feeding

• Currently participating to another clinical research protocol

• Individuals under legal protection or unable of giving their informed consent

• MRI scan contraindicated

• LUTATHERA® contraindicated