Clinical Trial Finder

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), or as soon as the diagnosis is made in case of hepatic invasion > 50% without waiting for tumour progression.

• - 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 (Intrauterine device, Progestin Pills, Combined Oral Contraceptives, Monthly Injectables, Progestin Injectables, Combined Patch, Combined Vaginal Ring, Female Sterilization, Vasectomy, Implants) 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 <30 g/L 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 or toxicity during one of the IV administrations leading to a reduction or cancellation of the following dose

Liver metastases of neuroendocrine tumors of gastro-entero-pancreatic origin are one of the most limiting factors of patient survival. Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs (SSA) such as LUTATHERA® represents now a major therapeutic option. As far as these metastases are mainly perfused by the hepatic artery, it could be relevant to deliver the treatment by intra-hepatic route, in order to achieve a maximized dose to the tumour when compared with a systemic conventional administration, while also reducing kidney and bone marrow toxicity. By using radiolabeled SSA for imaging and therapy, the present project aims to compare the uptake of 68Ga-DOTA-peptides after intra-hepatic versus intravenous injections for targeted liver metastases, as well as for dose limiting organs (kidney, spleen, healthy liver, bone marrow) and extra-hepatic lesions if present. The investigators will also evaluate whether the intra-hepatic infusion of one treatment dose of LUTATHERA® after conventional treatment by 4 intravenous administrations, is safe. Following 4 intravenous administrations of LUTATHERA® in GEP-NET with dominant liver metastases, patients who gave informed consent will be enrolled for 2 PET-scans, the first one after intra-hepatic injection of 68Ga-DOTA-peptides and the second one after intravenous injection for purpose of uptake comparison by 5 liver metastases chosen by radiologists on MRI. In 10 patients who meet a predefined enhancement ratio of 3, a 5th dose of LUTATHERA® will be administered by intra-arterial hepatic injection. An average enhancement ratio of 3.75 is expected from intra-arterial injection compared to intravenous results. Those 10 patients will be evaluated for 177Lu-DOTA-peptide activity and residence time by SPECT/CT imaging. Follow-up through 18 months will include clinical examination, MRI and CT scan, as usually performed in these clinical settings and progression

Arms

Experimental: 68Ga-DOTA-peptides PET/CT

68Ga-DOTA-peptides injections for targeted liver metastases in Positron emission tomography-computed tomography (PET/CT)

Experimental: LUTATHERA® by intra-arterial hepatic injection (IAH)

One treatment dose of LUTATHERA® by intra-arterial hepatic injection after conventional treatment by 4 intravenous administrations

Interventions

Procedure: - Positron emission tomography computed tomography (PET/CT) with Intra-hepatic (IAH) injection

Intra-hepatic injection of 68Ga-DOTA-peptides for targeted liver metastases in Positron emission tomography-computed tomography (PET/CT)

Procedure: - Positron emission tomography computed tomography (PET/CT) with Intravenous (IV) injection

intravenous injection of 68Ga-DOTA-peptides for targeted liver metastases in Positron emission tomography-computed tomography (PET/CT)

Drug: - LUTATHERA® by intra-arterial hepatic (IAH) injection

One treatment dose of LUTATHERA® by IAH injection for the 10 first patients with an PET/CT ratio greater then 3. The LUTATHERA® by intra-arterial hepatic injection treatment is realised after the conventional treatment by 4 intravenous administrations

Procedure: - Scan

Scans after completion of LUTATHERA® treatment injection