E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults |
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E.1.1.1 | Medical condition in easily understood language |
Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077560 |
E.1.2 | Term | Gastroenteropancreatic neuroendocrine tumor disease |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
68Ga-DOTA-peptides uptake (SUVmax) in 5 liver metastases on PET-scan obtained after intra-hepatic radiolabeled somatostatin analogs (SSA) infusion and on PET-scan obtained after intravenous radiolabeled SSA administration |
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E.2.2 | Secondary objectives of the trial |
- Safety profile for sub-group : safety of 177Lu-DOTA-peptide after intra-arterial hepatic administration - 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 - 68Ga-DOTA-peptide uptake (SUVmax) on extra-hepatic lesion after 68Ga-DOTA-peptides by arterial intrahepatic and intravenous injections - For the sub-group : 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 - For the sub-group : Efficacy evaluation of the fifth cycle of 177Lu-DOTA-peptide radiolabelled SSA therapy administered by intra-arterial hepatic infusion
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
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 |
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E.3 | Principal inclusion criteria |
• Histologically proven well differentiated neuroendocrine tumor (NET) of gastrointestinal or pancreatic origin (GEP). • Liver Metastatic disease dominant or exclusive and not amenable to surgical resection • Patients are progressive after treatment with cold somatostatin analogue (within 12 months according to RECIST) • Patient has received 4 standard of care LUTATHERA® cycles • 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 during and for 6 months post-treatment. • Patient´s signed written informed consent • Patient affiliated to a social security system
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E.4 | Principal exclusion criteria |
• 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. • 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
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E.5 End points |
E.5.1 | Primary end point(s) |
68Ga-DOTA-peptides uptake (Maximum Standardized Uptake Value) in 5 liver metastases on PET-scan obtained after intra-hepatic injection |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
68Ga-DOTA-peptides uptake (Maximum Standardized Uptake Value) in 5 liver metastases on PET-scan obtained after intravenous injection |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |