Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients

Study Overview
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Brief Summary
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The purpose of the study is to evaluate efficacy and safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide compared to targeted molecular therapy with Everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET).

Official Title
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A Prospective, Randomised, Controlled, Open-label, Multicentre Phase III Study to Evaluate Efficacy and Safety of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-Edotreotide Compared to Targeted Molecular Therapy With Everolimus in Patients With Inoperable, Progressive, Somatostatin Receptor-positive (SSTR+), Neuroendocrine Tumours of Gastroenteric or Pancreatic Origin (GEP-NET)

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: 177Lu-edotreotide PRRT
* Drug: Everolimus
* Other: Amino-Acid Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of well-differentiated neuro-endocrine tumour of non-functional gastroenteric origin (GE-NET) or both functional or non-functional pancreatic origin (P-NET) Measurable disease per RECIST 1.1 Somatostatin receptor positive (SSTR+) disease Progressive disease based on RECIST 1.1. criteria as evidenced by two morphological imaging examinations made with the same imaging method (either CT or MRI) Exclusion Criteria: Known hypersensitivity to edotreotide or everolimus Known hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus or any other Rapamycin derivative Prior exposure to any peptide receptor radionuclide therapy (PRRT) Prior therapy with mTor inhibitors Prior EFR (external field radiation) to GEP-NET lesions within 90 days before randomisation or radioembolisation therapy Therapy with an investigational compound and/or medical device within 30 days prior to randomisation Indication for surgical lesion removal with curative potential Planned alternative therapy (for the period of study participation) Serious non-malignant disease Clinically relevant renal, hepatic, cardiovascular, or haematological organ dysfunction, potentially interfering with the safety of the study treatments Pregnant or breast-feeding women Subjects not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g. persons institutionalised, incarcerated etc.).

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: 177Lu-edotreotide PRRT<br>177Lu-edotreotide (177Lu-DOTATOC) A maximum of four cycles of 7.5 ± 0.7 GBq (gigabequerel) 177Lu-edotreotide, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 4 cycles, 90 days apart (total duration: 270 days/9 months) | Drug: 177Lu-edotreotide PRRT<br>* PRRT using 177Lu-edotreotide will be performed 3-monthly. A maximum of four cycles will be administered.<br>* Other names: 177Lu-Edo;Other: Amino-Acid Solution<br>* The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of 25 g lysine and 25 g arginine diluted in 2000 mL of electrolyte solution, infused over 4 - 6 h, starting 30 - 60 min before PRRT<br>* Other names: Arginine-Lysine Solution;|
| Active Comparator: Everolimus<br>Everolimus (Afinitor ®) Doses: 10 mg/d Route of administration: Oral Duration of treatment: Continuous daily treatment until diagnosis of progression or End of Study (EOS) | Drug: Everolimus<br>* Everolimus will be adminstered as a standard dosis of 10 mg daily which may be reduced where required for acceptable tolerability.<br>* Other names: Afinitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | PFS will be assessed individually per patient from date of randomization until the date of first documented progression, assessed up to 30 months, primary outcome will be measured by CT/MRI every 12 weeks +/- 14 days | 12 weeks +/- 14 days, up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) | OS as secondary outcome measure will be assessed per patient from date of randomization until the date of death, whichever came first | every 3 months for a period of at least 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-functional and functional P-NET, non-functional GE-NET