Continuing Somatostatin Analogues Upon Progression in Neuroendocrine Tumour pAtients (SAUNA)

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

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)).

Study Overview

• Status: Recruiting
• Conditions: Gastroenteropancreatic Neuroendocrine Tumor
• Intervention / Treatment: Drug: Somatostatin analog

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marc U Peeters, MD; Phone Number: 4366 03821; Email: sauna@uza.be
• Study Contact Backup: Name: Timon Vandamme, MD; Email: timon.vandamme@uza.be

Study Locations

• Belgium
  • Antwerp, Belgium
    • Not yet recruiting
    • GZA
    • Contact: Isabelle Maurissen
  • Antwerpen, Belgium
    • Not yet recruiting
    • AZ Monica
    • Contact: Timon Vandamme
  • Antwerpen, Belgium
    • Not yet recruiting
    • Ziekenhuis Netwerk Antwerpen
    • Contact: Frank Van Fraeyenhove
  • Brussel, Belgium
    • Not yet recruiting
    • Cliniques Universitaires Saint-Luc
    • Contact: Ivan Borbath
  • Brussels, Belgium
    • Not yet recruiting
    • H.U.B.
    • Contact: Ioannis Karfis
  • Edegem, Belgium
    • Recruiting
    • Antwerp University Hospital
    • Contact: Timon Vandamme; Email: sauna@uza.be
  • Liège, Belgium
    • Not yet recruiting
    • Centre Hospitalier Universitaire Sart Tilman
    • Contact: Laurence Lousberg
  • Malle, Belgium
    • Not yet recruiting
    • AZ Voorkempen
    • Contact: Wim Demey
  • Antwerp
    • Brasschaat, Antwerp, Belgium
      • Not yet recruiting
      • AZ Klina
      • Contact: Wim Demey
    • Rumst, Antwerp, Belgium
      • Not yet recruiting
      • AZ Rivierenland
      • Contact: Marijke Ulenaers
  • East Flanders
    • Ghent, East Flanders, Belgium
      • Not yet recruiting
      • Ghent University Hospital
      • Contact: Karen Geboes
  • East-Flanders
    • Sint-Niklaas, East-Flanders, Belgium
      • Not yet recruiting
      • VITAZ
      • Contact: Willem Lybaert
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium
      • Not yet recruiting
      • University Hospital Leuven
      • Contact: Chris Verslype
  • Hainaut
    • Charleroi, Hainaut, Belgium
      • Not yet recruiting
      • Grand Hopital de Charleroi
      • Contact: Isabelle Sinapi
• Netherlands
  • Groningen, Netherlands
    • Not yet recruiting
    • UMC Groningen
    • Contact: Annemiek Walenkamp
  • Rotterdam, Netherlands
    • Not yet recruiting
    • Erasmus MC
    • Contact: Wouter de Herder
  • Gelderland
    • Arnhem, Gelderland, Netherlands
      • Not yet recruiting
      • Rijstate
      • Contact: Theo Van Voorthuizen
  • Limburg
    • Maastricht, Limburg, Netherlands
      • Not yet recruiting
      • Maastricht UMC+
      • Contact: Loes Latten-Jansen
  • North Brabant
    • Eindhoven, North Brabant, Netherlands
      • Not yet recruiting
      • Máxima Medisch Centrum
      • Contact: Wouter Dercksen
  • North Holland
    • Amsterdam, North Holland, Netherlands
      • Not yet recruiting
      • Amsterdam UMC
      • Contact: Heinz-Josef Klumpen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: somatostatin analogs continuation; 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; Somatostatin analog treatment every 4 weeks; Other Names: somatuline; sandostatin; lanreotide; octreotide
No Intervention: somatostatin analogs withdrawal; 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?

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

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Collaborators: Erasmus Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development; Belgium Health Care Knowledge Centre
• Investigators: Principal Investigator: Marc Peeters, MD, University Hospital, Antwerp

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2023
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2034

Study Registration Dates

• First Submitted: January 5, 2023
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: somatostatin analogues; neuroendocrine tumor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Physiological Effects of Drugs; Antineoplastic Agents; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Octreotide; Lanreotide; Somatostatin
• Other Study ID Numbers: EDGE 002337

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes