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

Radiotherapy Clinical Trial

— OPERANDI-NET  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06256705
• Other study ID #: APHP230280
• Status: Recruiting
• Phase: N/A
• Start date: March 25, 2024
• Est. completion date: September 25, 2029

Study information

• Verified date: March 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Catherine ANSQUER
• Phone: 00-33-2-40-08-41-36
• Email: catherine.ansquer[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 artificial intelligence (AI) and data augmentation, simultaneous 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 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 middle course of PRRT and at 1 year of the beginning of PRRT, in patients with advanced GEP-NETs treated with PRRT.

Description:

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 type of 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. PRRT is a recent therapeutic approach in GEP-NET. Due to its high efficacy, it has become one of the most relevant therapeutic option for patients with inoperable and/or metastatic GEP-NETs. PRRT exert antitumor effects based on radio-biological (DNA damages) and immunological mechanisms.

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 pertinent imaging 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 a completely innovative and holistic approach via PET-MRI guided therapy. Our hypothesis is that simultaneous 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 test 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 tracers according to the clinical indications to highlight metabolism or biological changes.

Until now, scientists could not integrate PET and MRI for simultaneous scanning because MRI's powerful magnets interfered with the imaging detectors on the PET scanner. PET and MRI scans have been conducted separately, and the separate images later merged. That merger, however, requires a complex computer process. The newly-available PET/MRI scanners can perform both types of scans at the same time to gather more information than merged PET and MRI scans. Beside the benefit of increased diagnostic and staging performance, it Improves safety from significantly reduced radiation exposure: Compared to PET/CT scans, PET/MRI exposes patients to about 50% less radiation.

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 artificial intelligence (AI) and data augmentation, simultaneous 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 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 middle course of PRRT and at 1 year of the beginning of PRRT, in patients with advanced GEP-NETs treated with PRRT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 25, 2029
• Est. primary completion date: March 25, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• According the MDT decision to refer to PRRT

1. Histologically confirmed diagnosis of unresectable GEP-NETs whatever the grade

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 and magnetic resonance imaging

4. SSTR+ disease, as evidenced by 68Ga-DOTATOC/PET performed within 2 months prior to inclusion (lesion uptake greater than liver physiological uptake)

5. The majority of the lesions and all RECIST v1.1 selected target lesion have to be SSTR+.

• Regardless of the number of previous treatment lines

• Karnofsky performance status scale = 60

• Live expectancy >6 months

• Patients = 18 years of age

• Patients who have signed a consent form to participate in the study, obtained prior to the start of any protocol related activities

Exclusion Criteria:

• Known pregnancy or breastfeeding women

• For women of childbearing age, pregnancy test (blood or urine)

• Known hypersensitivity to 177Lu, octreotate, DOTA, 68Ga, Edotreotide,

• Hypersensitivity to lysine, arginine, or any excipient of the nephroprotective amino acid solution (AAS) given concurrently with the 177Lu-DOTATATE infusion.

• Contraindication to MRI

• Prior external beam radiation therapy (EBRT) of GEP-NET lesions or liver selective internal radiation therapy within 12 weeks before inclusion

• Patient with severe hepatic and renal insufficiency

• Prior peptide receptor radionuclide therapy (PRRT)

• Absence of written informed consent from the patient

• Patient under guardianship or trusteeship

• No affiliation to social security (beneficiary or assignee) (as Patient on AME (state medical aid))

Related Conditions & MeSH terms

• Gastroenteropancreatic Neuroendocrine Tumor
• Intestinal Neoplasms
• Neuroendocrine Tumors
• Pancreatic Neoplasms
• Radiotherapy
• Stomach Neoplasms

Intervention

Other:
• Simultaneous 68Ga-DOTATOC PET-MRI
on month before first cycle of 177Lu-DOTATATE, after second cycle and one year after first cycle

Locations

Country	Name	City	State
France	Médecine nucléaire et Biophysique - Beaujon	Clichy
France	Pancréatologie et Oncologie Digestive - Beaujon	Clichy
France	Hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle - CHU Nantes	Nantes
France	Médecine nucléaire - CHU Nantes	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical response defined by the PFS as the time measured from the day of first administration of PRRT to first progression or death at 18 months, whichever occurs first		18 months after PRRT