Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy, safety & patient-reported outcomes of peptide receptor radionuclide therapy (PRRT) with 177Lu-Edotreotide as 1st or 2nd line of treatment compared to best standard of care in patients with well-differentiated aggressive grade 2 and grade 3, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin.

Official Title
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A Prospective, Randomised, Controlled, Open-label, Multicentre Study to Evaluate Efficacy, Safety and Patient-Reported Outcomes of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-Edotreotide Compared to Best Standard of Care in Patients With Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor-Positive (SSTR+), Neuroendocrine Tumours of GastroEnteric or Pancreatic Origin

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: 177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT
* Drug: CAPTEM (Capecitabine and Temozolomide)
* Other: Amino-Acid Solution
* Drug: Everolimus
* Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 18 years. Histologically confirmed diagnosis of unresectable, well-differentiated GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs). measurable site of disease per RECIST v1.1 (Response evaluation criteria in solid tumors) using contrast computed tomography (CT) / magnetic resonance imaging (MRI). Somatostatin receptor-positive (SSTR+) disease. Exclusion Criteria: Known hypersensitivity to Lutetium 177Lu, edotreotide, DOTA (dodecane tetraacetic acid), any of the comparators, or any excipient or derivative (e.g. rapamycin). Prior (Peptide Receptor Radionuclide Therapy) PRRT. Any major surgery within 4 weeks prior to randomization in the trial. Therapy with an investigational compound and/or medical device within 30 days or 7 half-life periods (whichever is longer) prior to randomization. Other known malignancies. Serious non-malignant disease. Renal, hepatic, cardiovascular, or hematological organ dysfunction, potentially interfering with the safety of the trial treatments. Pregnant or breastfeeding women. Patients not able to declare meaningful informed consent on their own or any other vulnerable population to that.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peptide Receptor Radionuclide Therapy (PRRT) Arm<br> | Drug: 177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT<br>* Peptide Receptor Radionuclide Therapy (PRRT) using 177Lu-edotreotide with a defined number of cycles will be administered.<br>* Other names: 177Lu-DOTATOC 177Lu-Edo;Other: Amino-Acid Solution<br>* The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of lysine and arginine diluted in an electrolyte solution.<br>* Other names: Arginine-Lysine Solution;|
| Active Comparator: CAPTEM(Capecitabine-Temozolomide), Everolimus, FOLFOX(Folinic acid + Fluorouracil + Oxaliplatin)<br> | Drug: CAPTEM (Capecitabine and Temozolomide)<br>* Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.<br>Drug: Everolimus<br>* Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.<br>Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin)<br>* Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | PFS (Progression-Free Survival), defined as the time from randomization until documented RECIST v1.1 (Response evaluation criteria in solid tumors) progression. | Every 12 weeks from randomization until disease progression or death whichever occurs earlier, during the time necessary to observe 148 Progression Free Survival (PFS) events. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | OS (Overall Survival), defined as the time from randomization until death; | Up to 2 years after disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GastroEnteroPancreatic, non-functional and functional GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NET)