SAUNA: Continuing Somatostatin Analogues Upon Progression in Neuroendocrine Tumour pAtients

Sponsor

University Hospital, Antwerp (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05701241

Collaborator

Erasmus Medical Center (Other), ZonMw: The Netherlands Organisation for Health Research and Development (Other), Belgium Health Care Knowledge Centre (Other)

270

Enrollment

Locations

Arms

131

Anticipated Duration (Months)

13.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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)).

Condition or Disease	Intervention/Treatment	Phase
Gastroenteropancreatic Neuroendocrine Tumor	Drug: Somatostatin analog	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

270 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2029

Anticipated Study Completion Date :

Apr 1, 2034

Arms and Interventions

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: lanreotide octreotide sandostatin somatuline
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somatostatin analogs withdrawal Somatostatin analog treatment (octreotide LAR 30 mg or lanreotide 120 mg) will be withdrawn for a duration of 18 months.

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:

lanreotide

octreotide

sandostatin

somatuline

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.

Outcome Measures

Primary Outcome Measures

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 [18 months after start second-line treatment]
PFS
The difference in time to deterioration (TTD) in patients continuing or stopping second-line therapy with SSAs per substudy [18 months after start second-line treatment]
TTD

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country
1	AZ Klina	Brasschaat	Antwerp	Belgium
2	AZ Rivierenland	Rumst	Antwerp	Belgium
3	Ghent University Hospital	Ghent	East Flanders	Belgium
4	VITAZ	Sint-Niklaas	East-Flanders	Belgium
5	University Hospital Leuven	Leuven	Flemish Brabant	Belgium
6	Grand Hôpital de Charleroi	Charleroi	Hainaut	Belgium
7	AZ Monica	Antwerpen		Belgium
8	Ziekenhuis Netwerk Antwerpen	Antwerpen		Belgium
9	GZA	Antwerp		Belgium
10	H.U.B.	Brussels		Belgium
11	Cliniques Universitaires Saint-Luc	Brussel		Belgium
12	Antwerp University Hospital	Edegem		Belgium
13	Centre Hospitalier Universitaire Sart Tilman	Liège		Belgium
14	AZ Voorkempen	Malle		Belgium
15	Rijstate	Arnhem	Gelderland	Netherlands
16	Maastricht UMC+	Maastricht	Limburg	Netherlands
17	Maxima Medisch Centrum	Eindhoven	North Brabant	Netherlands
18	Amsterdam UMC	Amsterdam	North Holland	Netherlands
19	UMC Groningen	Groningen		Netherlands
20	Erasmus MC	Rotterdam		Netherlands