Lutetium (177Lu) oxodotreotide for Gastroenteropancreatic neuroendocrine tumour (GEP-NET)

Inclusion criteria

• {"criterion_text":"- Histologically proven well differentiated neuroendocrine tumor (NET) of gastrointestinal or pancreatic origin (GEP)"}
• {"criterion_text":"- Patient´s signed written informed consent"}
• {"criterion_text":"- Patient affiliated to a social security system"}
• {"criterion_text":"- Liver Metastatic disease dominant or exclusive and assessable by RECIST 1.1, and not amenable to surgical resection after the 4 cycles"}
• {"criterion_text":"- Patients are progressive after treatment with cold somatostatin analog (within 12 months according to RECIST), or as soon as the diagnosis is made in case of hepatic invasion > 50% without waiting for tumour progression"}
• {"criterion_text":"- Patient has received 4 standard of care LUTATHERA® cycles"}
• {"criterion_text":"- ECOG performance status 0-2"}
• {"criterion_text":"- Adequate kidney and liver function: creatinine clearance ≥ 50 mL/min, ALT/AST ≤ 2,5x the upper limit of normal"}
• {"criterion_text":"- With no evidence of hematologic alteration after 4 LUTATHERA® cycles: hemoglobin ≥ 8 g/dL, neutrophils ≥ 1500/ mm3, platelets ≥ 75.000/mm3"}
• {"criterion_text":"- Age ≥ 18 years, no superior limit"}
• {"criterion_text":"- Highly effective contraception for women of childbearing potential (Intrauterine device, Progestin Pills, Combined Oral Contraceptives, Monthly Injectables, Progestin Injectables, Combined Patch, Combined Vaginal Ring, Female Sterilization, Vasectomised partner, sexual abstinence, Implant). Contraception for men (condom) or their sexual partner (effective contraception) (CTFG recommandations : https://www.hma.eu/fileadmin/dateien/Human_Medicines/01- About_HMA/Working_Groups/CTFG/2020_09_HMA_CTFG_Contraceptio n_guidance_Version_1.1_updated.pdf). Contraception must be maintained for at least 7 months after the last LUTATHERA ® injection for women with childbearing capacity and at least 4 months for men who have female partners with childbearing capacity"}

Exclusion criteria

• {"criterion_text":"- 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)"}
• {"criterion_text":"- Individuals under legal protection or unable of giving their informed consent"}
• {"criterion_text":"- MRI scan contraindicated"}
• {"criterion_text":"- LUTATHERA® contraindicated or toxicity during one of the IV administrations leading to a reduction or cancellation of the following dose"}
• {"criterion_text":"- Or no residual uptake according to standard 177-Lu tomoscintigraphy performed in the clinical routine 24 hours after the last LUTATHERA IV treatment"}
• {"criterion_text":"- Carcinoid heart disease (LVEF < 40%)"}
• {"criterion_text":"- Dominant or threatening extrahepatic metastases or that may affect vital prognosis"}
• {"criterion_text":"- 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…)"}
• {"criterion_text":"- Serum albumin <30 g/L unless prothrombin time is within the normal range."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Pregnancy or breast feeding"}
• {"criterion_text":"- Currently participating to another category 1 or 2 clinical research protocol"}

Primary endpoints

• {"endpoint_text":"- 68Ga-DOTA-peptides uptake (Maximum Standardized Uptake Value) in up to 5 liver metastases on PET-scan obtained after intra-hepatic injection","definition_or_measurement_approach":"Measurement of SUVmax on PET-scan in up to 5 liver metastases; PET imaging performed after intra-hepatic arterial (IAH) administration and after intravenous (IV) administration for comparison."}

Secondary endpoints

• {"endpoint_text":"- Safety profile : safety of 177Lu-DOTA-peptide after intra-arterial hepatic administration","definition_or_measurement_approach":"Assessment of adverse events frequency and severity using CTCAE v4.03 collected via clinical, biological and imaging parameters across 7 follow-up visits over a period of 18 months."}
• {"endpoint_text":"- 68Ga-DOTA-peptide uptake (SUVmax) on dose limiting organs (kidney, spleen, healthy liver, bone marrow) after 68Ga-DOTA-peptides by arterial intrahepatic and intravenous injections","definition_or_measurement_approach":"Measurement and comparison of SUVmax in dose-limiting organs (kidney, spleen, healthy liver, bone marrow) on PET imaging after IAH and IV administrations."}
• {"endpoint_text":"- 68Ga-DOTA-peptide uptake (SUVmax) on extra-hepatic lesion (if present) after 68Ga-DOTA-peptides by arterial intrahepatic and intravenous injections","definition_or_measurement_approach":"Measurement of SUVmax on up to 5 representative extra-hepatic lesions (if present) from PET images after IV and IAH injection to compare uptake."}
• {"endpoint_text":"- Estimate the lesional and organ (kidney, spleen, healthy liver, bone marrow) absorbed doses after 177Lu-DOTA-peptide administration by intra-arterial hepatic and intravenous injections","definition_or_measurement_approach":"Dosimetry estimating activity and residence time of 177Lu-DOTA-peptide in preselected hepatic targets, extra-hepatic lesions and healthy organs to compute absorbed doses."}
• {"endpoint_text":"- Efficacy evaluation of the fifth cycle of 177Lu-DOTA-peptide therapy administered by intra-arterial hepatic infusion according to RECIST1.1 criteria","definition_or_measurement_approach":"Objective response rate and progression-free survival assessed per RECIST 1.1; imaging schedule: hepatic MRI every 3 months and CT scan every 6 months during an 18-month follow-up; objective response defined as proportion of patients with complete or partial response at 18 months."}

France

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

04-11-2024

Processing Time Days

18

Number Of Sites

5

Number Of Participants

23

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Bordeaux

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France