Multi-modal Characterisation of Gastroenteropancreatic Neuroendocrine Tumours (GEP-NETs) Treated with Targeted Radionuclide Therapy (TRT): Prospective Interventional Multicentre National Cohort

Study Purpose

Operandi project aims to address unmet clinical needs in the current management of GEP-NETs treated with PRRT by exploring new opportunities provided by imaging-based (AI algorithms) and data augmentation, simultaneous 68Ga-DOTATOC PET-MRI imaging, and novel approaches to increase patient selection and PRRT efficacy (genomic profiling, radiopotentiators, and new radionuclides). The study aim to identify predictive and early markers indicative of PRRT effectiveness based on a large prospective cohort of GEP-NET patients. This cohort will be used to uncover relevant predictive signatures within the morphological, functional, and molecular imaging data using novel imaging-based AI approaches with a new patient imaging pathway including simultaneous 68Ga-DOTATOC PET-MRI. Considering this global objective, the objective of this clinical research protocol is to provide clinical, molecular and imaging data in a prospective standardized study, notably by performing systematic PET-MRI at baseline, at mid course of PRRT and 1 year after PRRT initiation, in patients with advanced GEP-NETs treated with PRRT.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - According the MDT decision to refer to PRRT.
1. Histologically confirmed diagnosis of unresectable GEP-NETs whatever the grade or NETs of unknown primary but suspected of GEP origin. 2. Metastastic and progressive according RECIST 1.1 criteria. 3. At least 1 measurable site of disease per RECIST v1.1 using contrast-enhanced CT or magnetic resonance imaging. 4. SSTR+ disease, as evidenced by PET-DOTATOC performed within 4 months prior to inclusion (lesion uptake greater than liver physiological uptake) 5. The majority of the lesions and all RECIST 1.1 selected target lesion have to be SSTR+.
  • - Karnofsky performance status scale ≥ 60.
  • - Live expectancy >6 months.
  • - Patients ≥ 18 years of age.

Exclusion Criteria:

  • - Known pregnancy or breastfeeding women.
  • - Known hypersensitivity to 177Lu, octreotate, DOTA, 68Ga, Edotreotide, - Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective amino acid solution (AAS) given concomitantly to the 177Lu-DOTATATE infusion.
  • - Contraindication to MRI and technical impossibility of MRI.
  • - Prior external beam radiation therapy (EBRT) of GEP-NET lesions or liver selective internal radiation therapy within 12 weeks before inclusion, if extensive.
  • - Other systemic antitumor treatment (non-radioactive, excluding somatostatin analogues) not interrupted for at least 4 weeks.
  • - Mixed Neuroendocrine-Non-endocrine Neoplasms (MiNEN) - Neuroendocrine carcinoma.
  • - Uncontrolled brain metastasis for at least 3 months.
  • - NYHA 3 or 4 heart failure.
  • - Inability to discontinue delayed-acting somatostatin analogues at least 28 days prior the PRRT or rapid-acting somatostatin analogues at least 24 hours prior the PRRT.
  • - Non-adequate bone marrow, liver and renal function within 1 month prior the PRRT as assessed by the following laboratory tests: - Platelet count < 75,000/mm3.
  • - Haemoglobin ≤ 8,0 g/dL.
  • - Total bilirubin > 3 ULN.
  • - Neutrophils < 1000/mm3.
  • - Prothrombin time < 70% unless albumin > 30g/L.
  • - Albumin <30g/L unless prothrombin time > 70 % - Glomerular Filtration Rate (GFR) < 35 mL/min/1.73 m2.
  • - Prior peptide receptor radionuclide therapy (PRRT) - Other progressive cancer excluding in situ cervical cancer and basal or squamous cell skin cancer within the last 3 years.
  • - Patient refusal to give written informed consent.
  • - Subject deprived of freedom, subject under a legal protective measure.
  • - No affiliation to a social security regimen or CMU.
- Patient under State Medical Aid

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06256705
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Assistance Publique - Hôpitaux de Paris
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Gastroenteropancreatic Neuroendocrine Tumor, Radiotherapy
Additional Details

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are considered rare neoplasms. Their incidence has been increasing over the last few decades, and due to generally prolonged survival of patients, the prevalence of GEP-NETs is higher than the combined prevalence of other more common gastrointestinal cancers, including oesophageal cancers, gastric adenocarcinomas, and pancreatic adenocarcinomas. Prognosis is related to several factors and especially to liver tumour involvement. Peptide Receptor Radionuclide Therapy (PRRT) is a targeted radionuclide therapy that has been used in the treatment of patients with GEP-NETs for over two decades. The molecular target for PRRT in NETs is the somatostatin receptor (SSTR), mainly the subtype 2, which is highly expressed in most of these tumours. The 177lu-DOTATATE, a radiolabelled somatostatin analog, has reached a wide use due to a combination of high anti-tumour activity and a low level of toxicity. 177Lu-DOTATATE was granted marketing authorisation by the European Medicines Agency in 2017 and by the Food and Drug Administration in 2018 for the treatment of GEP-NETs. Due to its high efficacy, it has become one of the most relevant therapeutic option for patients with inoperable and/or metastatic GEP-NETs. Response evaluation

  • - PRRT exerts antitumor effects based on radio-biological (DNA damages) and immunological mechanisms.
While highly promising, patient stratification and early identification of responders are currently insufficient due to the lack of reliable biomarkers, either non-invasive or invasive. Furthermore, prior therapy-induced DNA damages may lead to tumour resistance, therefore reducing PRRT efficacy. Hence, the absence of a personalized treatment strategy is an unmet need for patients with GEP-NETs. This may result in survival disadvantage for non-responders, who could benefit otherwise from early treatment change, with expected more favourable outcomes. Simultaneous PET-MRI: OPERANDI project proposes an innovative and holistic approach via PET-MRI guided therapy with somatostatin analogues (68Ga-DOTATOC). Our hypothesis is that simultaneous 68Ga-DOTATOC PET-MRI imaging provides more robust non-invasive predictive biomarkers than classical approach. This requires technological development of PET-MRI, with most methodological challenges being attenuation correction, reducing the impact of organ motion due to respiration and cardiac motion, and minimizing truncation and susceptibility artefacts. A PET/MRI scan is a two-in-one exam that combines images from a positron emission tomography (PET) scan and a magnetic resonance imaging (MRI) scan. This new hybrid technology harnesses the strengths of PET and MRI to produce some of the most highly detailed images currently available. MRI scans use a strong (1.5 to 3T for clinical use) magnetic field to produce detailed morphologic images and some sequences provide functioning information (such as diffusion-weighted, dynamic contrast-enhanced, MR elastography sequence). PET scan use radiotracers according to the clinical indications to highlight metabolism or biological changes. The most common radiotracer that has been used so far is fluorodeoxyglucose (FDG), which detects metabolically active malignant lesions. Gallium-68-labeled somatostatin analogues (including 68Ga DOTATOC) are differentiation markers in NETs and are a prerequisite for verifying sufficient SSTR2 expression and selecting patients for PRRT. The OPERANDI project aims to address unmet clinical needs in the current management of GEP-NETs treated with PRRT by exploring new opportunities provided by imaging-based (AI algorithms) and data augmentation, simultaneous 68Ga-DOTATOC PET-MRI imaging, and novel approaches to increase patient selection and PRRT efficacy (genomic profiling, radiopotentiators, and new radionuclides). The study aim to identify predictive and early markers indicative of PRRT effectiveness based on a large prospective cohort of GEP-NET patients. This cohort will be used to uncover relevant predictive signatures within the morphological, functional, and molecular imaging data using novel imaging-based AI approaches with a new patient imaging pathway including simultaneous 68Ga-DOTATOC PET-MRI.

Arms & Interventions

Arms

Experimental: PET-MRI

PET-MRI added in care pathway

Interventions

Other: - Simultaneous 68Ga-DOTATOC PET-MRI

on month before first cycle of 177Lu-DOTATATE, after second cycle and one year after first cycle

Contact a Trial Team

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International Sites

Clichy, France

Status

Recruiting

Address

Médecine nucléaire et Biophysique - Beaujon

Clichy, , 92110

Site Contact

LEBTAHI Rachida, Pr

[email protected]

01 40 87 51 69

Clichy, France

Status

Recruiting

Address

Pancréatologie et Oncologie Digestive - Beaujon

Clichy, , 92110

Site Contact

Louis DE MESTIER

[email protected]

01 40 87 52 41

Nantes, France

Status

Active, not recruiting

Address

Hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle - CHU Nantes

Nantes, , 44000

Médecine nucléaire - CHU Nantes, Nantes, France

Status

Recruiting

Address

Médecine nucléaire - CHU Nantes

Nantes, , 44000

Site Contact

Catherine ANSQUER, Dr

[email protected]

02 40 08 41 44

Paris, France

Status

Active, not recruiting

Address

Service de Médecine Nucléaire, Groupe Hospitalier Bichat-Claude Bernard

Paris, , 75018

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