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

Overview

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).

Full Title of Study: “”Imaging With 68Ga-DOTA-peptides and Peptide Receptor Radionuclide Therapy With 177Lu-DOTA-peptides of Gastroenteropancreatic Neuroendocrine Tumors: Interest of Intra-arterial Hepatic Infusion in Patients With Dominant Liver Metastases””

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 1, 2023

Detailed Description

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. We 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. (Based on literature data, an average enhancement ratio of 3.75 is expected from intra-arterial injection compared to intravenous results; Kratochwil 2010). 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

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

Arms, Groups and Cohorts

  • 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

Clinical Trial Outcome Measures

Primary Measures

  • Standardized uptake value (SUVmax) on liver metastases
    • Time Frame: Day 0 (First PET/CT)
    • Standardized uptake value (SUVmax) on liver metastase obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on liver metastases
    • Time Frame: Day 3 (second PET/CT)
    • Standardized uptake value (SUVmax) on liver metastase obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides

Secondary Measures

  • Standardized uptake value (SUVmax) on healthy liver
    • Time Frame: Day 0 (First PET/CT)
    • Standardized uptake value (SUVmax) on healthy liver obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on healthy liver
    • Time Frame: Day 3 (second PET/CT)
    • Standardized uptake value (SUVmax) on healthy liver obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on kidneys
    • Time Frame: Day 0 (First PET/CT)
    • Standardized uptake value (SUVmax) on kidneys obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on kidneys
    • Time Frame: Day 3 (second PET/CT)
    • Standardized uptake value (SUVmax) on kidneys obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on bone marrow
    • Time Frame: Day 0 (First PET/CT)
    • Standardized uptake value (SUVmax) on bone marrow obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on bone marrow
    • Time Frame: Day 3 (second PET/CT)
    • Standardized uptake value (SUVmax) on bone marrow obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on spleen
    • Time Frame: Day 0 (First PET/CT)
    • Standardized uptake value (SUVmax) on spleen obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on spleen
    • Time Frame: Day 3 (second PET/CT)
    • Standardized uptake value (SUVmax) on spleen obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on associated extra-hepatic metastases
    • Time Frame: Day 0 (First PET/CT)
    • Standardized uptake value (SUVmax) on associated extra-hepatic metastases obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • Standardized uptake value (SUVmax) on associated extra-hepatic metastases
    • Time Frame: Day 3 (second PET/CT)
    • Standardized uptake value (SUVmax) on associated extra-hepatic metastases obtained on PET/CT imaging after injection of 68Ga-DOTA-peptides
  • 177Lu-DOTA-peptide dosimetry
    • Time Frame: Day 18
    • Absorbed dose in different tissue of the 5 hepatic targets, possible extra-hepatic lesions and healthy organs (healthy liver, kidney, bone marrow, spleen)

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital, Bordeaux
  • Collaborator
    • Advanced Accelerator Applications
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Ghoufrane TLILI, Principal Investigator, University Hospital, Bordeaux
  • Overall Contact(s)
    • Ghoufrane TLILI, Dr, 05 57 65 64 08, ghoufrane.tlili@chu-bordeaux.fr

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.