In neuroendocrine tumors (NET) of the stomach, intestine and pancreas, hormone therapy with somatostatin analogues (SSA) is frequently used as the first-line treatment when the disease cannot be cured. This treatment is usually continued for life in hormonally active NET. However, it is currently unclear whether it is useful to continue treatment with hormone therapy in the majority of patients with a hormonally inactive NET if the tumor progressed under SSA and therefore additional treatment is needed.
The purpose of this international clinical trial is to investigate the efficacy of continuing hormone therapy after growth of a NET of the stomach, intestine or pancreas that is not hormonally active. The study will take place among 270 patients at 21 hospitals in Belgium and the Netherlands. Patients will be able to choose one of two common forms of second-line therapy, peptide receptor radionuclide therapy or targeted therapy, after consultation with their physician. Patients will then be randomly allocated to continuing or discontinuing the hormone therapy during second-line therapy. Study participants will continue or discontinue hormone therapy for 18 months, after which they will be followed up by telephone for five more years regarding the status of their disease.
| Title |
Continuing Somatostatin Analogues Upon progression in Neuroendocrine tumour pAtients |
|
Participants (P) |
Patients with histologically-proven, non-functional, well-differentiated WHO 2019 grade 1-2 neuroendocrine tumours of gastroenteropancreatic origin with disease progression on first-line somatostatin analogues |
|
Intervention (I) |
Continue somatostatin analogues alongside second-line systemic therapy consisting of either peptide receptor radionuclide therapy (PRRT – substudy 1) or targeted therapy (TT – substudy 2) |
|
Control (C) |
Withdraw somatostatin analogues while starting second-line systemic therapy |
|
Outcome (O) |
To assess 1) the difference in progression free survival (PFS) between patients continuing or stopping SSA after initiation of second-line therapy, as assessed by blinded local radiologists on cross-sectional imaging per substudy (per RECIST 1.1) 2) the difference in time to deterioration (TDD) in patients continuing or stopping SSA treatment after initiating second-line therapy per substudy. TDD is defined as time from randomisation to the first decrease from baseline on the Global Health component of the EORTC QLQ C-30 questionnaire by at least 10 points (on a 100-point scale), with no further increase above this threshold, or death. |
|
Trial Design |
Multi-national, multi-centre, open-label, randomised, controlled, pragmatic clinical trial in patients with advanced, non-functional GEP NETs with progressive disease on first-line therapy with somatostatin analogues. Eligible patients will be divided into two substudies according to the second-line therapy of choice (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 SSAs at the start of second-line systemic therapy. Stratification will occur according to study site and according to the Ki67 value (<10% (G1 and low G2) and ≥10% (high G2)). |
|
Sample Size |
270 study participants |
|
Trial duration |
72 months (+ 5 years long term follow-up) |
|
Budget |
2.67Mio for whole study and 1.40Mio in Belgium |
| Sponsor | Antwerp University Hospital |
| Chief Investigator | Prof. Dr. Timon Vandamme |
| National Coordinator in the Netherlands | Prof. dr. W.W. de Herder (Erasmus MC, Rotterdam) |
| Number of participating sites | 21 (15 in Belgium and 6 in the Netherlands) |
