Neuroendocrine tumours (NETs) are slow growing cancers, which commonly present as metastatic incurable disease. Some neuroendocrine tumours, termed functional NETs, overproduce hormones which result in a variety of symptoms. However, approximately 75% of NETs are considered non-functional meaning that they do not result in hormone overproduction. The main treatment for both functional and non-functional NETs is somatostatin analogues (SSA, a type of inhibitory hormone). These drugs slow tumour growth and reduce hormone production. Over time, the majority of patients will experience tumour growth despite treatment with SSA therapy. When this occurs, the addition of Peptide Receptor Radionuclide Therapy (PRRT, a type of targeted radiotherapy) in combination with ongoing SSA therapy is given. However, it is not known if continuing SSA therapy after commencement of PRRT is beneficial or not.
The aim of this study is to estimate the outcomes of patients with grade 1 and 2 well differentiated mid, hind-gut or pancreatic neuroendocrine tumours who have progressed on SSA therapy and receive subsequent PRRT with or without concurrent SSA.
Adults over 18 years of age with well or moderately differentiated mid or hindgut neuroendocrine tumour, or pancreatic neuroendocrine tumour, metastatic and inoperable, demonstrating progression despite SSA treatment of sufficient disease magnitude to warrant PRRT as determined by the treating clinician and/or the NET Multidisciplinary Team (MDT).
Must have measurable disease on triphasic CT/MRI as per RECIST 1.1.
Ki67 ≤ 20% AND mitotic count 20 per HPF (i.e., WHO grade 1 or 2)
Patient has been receiving growth-controlling doses of SSA for at least 12 weeks prior to study entry. This is a minimum of 30 mg Octreotide or120mg lanreotide monthly.
This study is for pancreatic, mid-gut and hind-gut NET only. Gastric and lung NETs are excluded
Any patient on an SSA dose lower than the standard growth-control dose. Patients must have been on octreotide 30 mg or lanreotide 120 mg for at least 3 months prior to study entry.
Prior chemotherapy or targeted therapy (e.g., everolimus). Patients who have received prior local therapy, including external beam radiotherapy and liver directed therapy prior to or during SSA therapy are eligible.
Any contraindication to PRRT, as per local institutional practice.
Parallel
Cessation of somatostatin analogues
DrugPatients randomised to cease SSA will receive their last SSA injection ≥28 days prior to their first cycle of PRRT and will remain off SSA for the duration of the study. If there is concern from the treating team that a patient may experience a carcinoid flare after PRRT, then short acting octreotide is allowed to be used to control any symptoms.
Continuation of somatostatin analogues
DrugPatients randomised to continue SSA will receive a SSA injection ≥28 days prior to their first cycle of PRRT, during PRRT and will continue receiving SSA every 4 weeks after PRRT.
20-month progression free survival rate after PRRT
Estimate the 20-month progression free survival rate after PRRT in patients who cease and who continue SSA.
Assess the barriers which would impede the feasibility of a subsequent phase 3 trial
1. Proportion of participants that remained on the SSA cessation arm for the duration of the 20-month study follow up (patient acceptance of SSA cessation). 2. Rate of recruitment: ability to complete recruitment over the 24-month recruitment period
Measure Quality of life using the European Organisation For Research And Treatment Of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30) scales
Responses to the QLQ-C30 scale from 0-100 using EORTC guidelines, with higher scores reflecting better level of functioning.
Measure Quality of life using the EORTC QLQ-GINET21 scales
Responses to the QLQ-GINET21 scale from 0-100 using EORTC guidelines, with higher scores reflecting more severe symptoms.
Cost-effectiveness of SSA therapy cessation
Access to Medicare and PBS data to asses use of other healthcare providers, diagnostic tests and imaging services funded via public health care systems and use of pharmaceutical services respectively.
Psycho-oncological impacts of SSA therapy cessation: Decision Regret
Psycho-oncological impacts of SSA therapy cessation using the self-reported measures of Decision Regret Scale from 1 - 5 (1-Strongly Agree, 2-Agree, 3-Neither Agree Nor Disagree, 4-Disagree, 5-Strongly Disagree)
Exploratory analyses
Exploratory analyses including, but not limited to: Define and validate NET tissue and circulating biomarkers with a particular focus on miRNA.
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Australasian Gastro-Intestinal Trials Group
Lead sponsor
Canadian Cancer Trials Group
Collaborator
