Continuing Somatostatin Analogues Upon Progression in Neuroendocrine Tumour pAtients

Study Overview
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Brief Summary
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The SAUNA trial is a multi-national, multi-centre, open-label, randomised, controlled, pragmatic clinical trial in patients with advanced, non-functional gastroenteropancreatic (GEP) neuroendocrine tumours (NET) with progressive disease on first-line therapy with somatostatine analogues (SSA). Eligible patients will be divided into two substudies according to the second-line therapy of choice (peptide receptor radionuclide therapy (PRRT) or targeted therapy, at the discretion of the local investigator). Patients within each substudy will be randomised 1:1 between continuation or withdrawal from SSA at the start of second-line systemic therapy. Stratification will occur according to study site and according to the Ki67 value (below 10% (grade 1 and low grade 2) and equal to or above 10% (high grade 2)).

Official Title
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Continuing Somatostatin Analogues Upon Progression in Neuroendocrine Tumour pAtients - The SAUNA Trial

Conditions
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Gastroenteropancreatic Neuroendocrine Tumor

Intervention / Treatment
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* Drug: Somatostatin analog


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Written informed consent prior to any study-related procedures Eastern Cooperative Oncology Group (ECOG) performance status ≤2, Histologically-proven diagnosis of locally advanced or metastatic, non-functional, well-differentiated World Health Organisation 2019 grade 1-2 GEP NET Documented radiological disease progression on first-line SSA treatment For targeted therapy substudy: indication to start with either sunitinib or everolimus as second-line therapy, according to local investigator For PRRT substudy: indication to start with PRRT with Lutetium (177Lu) oxodotreotide as second-line therapy, according to local investigator Exclusion Criteria: Indication for chemotherapy treatment of GEP NET in second-line Presence of poorly differentiated grade 3 neuroendocrine carcinoma (NEC), well-differentiated grade 3 NET or rapidly progressive NET Prior treatment with everolimus, sunitinib or PRRT Contra-indication, proven allergy or other indication than functional NET for the use of a SSA Patient showing progressive disease while being on a lower than the registered dose Functional NET, defined as the presence of clinical and biochemical evidence of a hormonal NET-related syndrome Patient undergoing palliative, systemic oncological treatment for other malignancy than GEP NET Concurrent anti-cancer treatment in another investigational trial Any abnormal findings at baseline, clinical finding, including psychiatric and behavioural problems, or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study Pregnant or lactating patient at screening or if the patient wishes to get pregnant during treatment phase of the trial

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 |
| --- | --- |
| Active Comparator: somatostatin analogs continuation<br>Somatostatin analog (octreotide long-acting release (LAR) 30 mg or lanreotide 120 mg) will be given every four weeks for a duration of 18 months. | Drug: Somatostatin analog<br>* Somatostatin analog treatment every 4 weeks<br>* Other names: somatuline;|
| No Intervention: somatostatin analogs withdrawal<br>Somatostatin analog treatment (octreotide LAR 30 mg or lanreotide 120 mg) will be withdrawn for a duration of 18 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the difference in progression-free survival (PFS) in patients continuing or stopping second-line therapy with SSAs, as assessed by the blinded local investigator on cross-sectional imaging, according to RECIST 1.1 criteria per substudy | PFS | 18 months after start second-line treatment | 
| The difference in time to deterioration (TTD) in patients continuing or stopping second-line therapy with SSAs per substudy | TTD | 18 months after start second-line treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival rate according to RECIST 1.1 | PFS rate | 18 months after start second-line treatment | 
| The difference in a pooled progression-free survival of both substudies | PFS | 18 months after start second-line treatment | 
| The difference in a pooled time to deterioration of both substudies | TTD | 18 months after start second-line treatment | 
| Overall survival (OS) per substudy and pooled over both substudies | OS | Time until death; assessed up to 5 years after treatment phase | 
| Overall survival pooled over both substudies | OS | Time until death; assessed up to 5 years after treatment phase | 
| Response rates (RR) per substudy | RR | 18 months after start second-line treatment | 
| Response rates over both substudies | RR | 18 months after start second-line treatment | 
| Quality of life (QoL) measurement with questionnaire | QoL measurement with 30-item Quality of Life Questionnaire (QLQ-C30) | End of study (6.5 years after start second-line treatment) | 
| Quality of life (QoL) measurement with questionnaire | QoL measurement with 21-item QoL questionnaire in the gut, pancreas and liver neuroendocrine tumours (QLQ-GINET21) | End of study (6.5 years after start second-line treatment) | 
| Quality of life (QoL) measurement with questionnaire | QoL measurement with EuroQol-5 Dimensions-5 Level questionnaire | End of study (6.5 years after start second-line treatment) | 
| Cost-effectiveness | Health technology assessment (HTA) analysis | End of study (6.5 years after start second-line treatment) | 
| Drug safety | Safety will be reported in terms of incidence and severity of (serious) adverse events | 18 months after start second-line treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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somatostatin analogues, neuroendocrine tumor