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.
Neuroendocrine tumours commonly originate from the gut and metastasise widely including to the liver, lymph nodes and bones. Originally called "carcinoid tumours", these cancers are most commonly treated with somatostatin analogues (SSA) first line. These analogues treat carcinoid syndrome and slow tumour growth. Despite SSA therapy, progression develops over time. Upon progression, peptide receptor radionuclide therapy (PRRT) is the next standard therapeutic option. After PRRT is initiated, it is unclear if continuing SSA injections is beneficial. There are reasons to believe it might be necessary to continue SSAs, but other reasons to believe they should cease. Given that SSA injections are expensive and associated with side effects, this study aims to clarify the utility of continuing SSA injections after progression on SSA therapy and commencement of PRRT. STOPNET aims to explore outcomes in grade 1 and 2 mid, hind gut or pancreatic neuroendocrine tumours, that have progressed on SSA therapy, are eligible to receive PRRT and in whom the SSA is either continued or ceased after PRRT is commenced. The two primary objectives include 1. To estimate the 20-month progression free survival rate after PRRT commencement in patients who cease and who continue SSA. 2. Feasibility as measured by: 1. Recruitment rate and 2. Patient acceptance of ceasing and staying off SSA over the 20 month follow up period. The study design of STOPNET is prospective, randomised, non-comparative, open label, multicentre phase II study. Patients meeting the inclusion and exclusion criteria will be randomised, prior to commencing PRRT, to either continue or cease SSA treatment. Randomisation will occur centrally in REDCap by the AGITG STOPNET study team. Randomisation will be 2:1 (the majority being randomised to cease SSA) and will be stratified by WHO tumour grade (1 V 2), sites of metastases (visceral only verse visceral and bone) and institution.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
Patients 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.
Patients 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.
Royal North Shore Hospital
Sydney, New South Wales, Australia
RECRUITINGWollongong Hospital
Wollongong, New South Wales, Australia
RECRUITINGRoyal Brisbane and Womens Hospital
Brisbane, Queensland, Australia
RECRUITINGCairns Hospital
Cairns, Queensland, Australia
RECRUITINGToowoomba Hospital
Toowoomba, Queensland, Australia
RECRUITINGThe Queen Elizabeth Hospital
Adelaide, South Australia, Australia
RECRUITINGPeter MacCallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGKalgoorlie Health Campus
Kalgoorlie-Boulder, Western Australia, Australia
RECRUITINGFiona Stanley Hospital
Perth, Western Australia, Australia
RECRUITINGCross Cancer Institute
Edmonton, Alberta, Canada
RECRUITING...and 7 more locations
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.
Time frame: 20 months
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
Time frame: 20 months
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.
Time frame: 20 months
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.
Time frame: 20 months
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.
Time frame: The MBS/PBS data will be obtained for the period six months prior to study entry, and until the end of 2 years follow-up post PRRT for patients who have provided consent.
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)
Time frame: 20 months
Psycho-oncological impacts of SSA therapy cessation: Fear of Cancer Progression
Psycho-oncological impacts of SSA therapy cessation using the self-reported measures of the Fear of Cancer Progression Scale from 1 - 5 (1-Never, 2-Seldom, 3-Sometimes, 4-Often, 5-Very often)
Time frame: 20 months
Psycho-oncological impacts of SSA therapy cessation: Decisional Conflict
Psycho-oncological impacts of SSA therapy cessation using the self-reported measures of the Decisional Conflict Scale from 0 - 4 (0-Strongly Agree, 1-Agree, 2-Neither Agree Nor Disagree, 3-Disagree, 4-Strongly Disagree)
Time frame: 20 months
Time to commencement of subsequent therapy
Time to commencement of subsequent therapy (e.g re-challenge with PRRT, liver directed therapies, chemotherapy, targeted therapies)
Time frame: 20 months
Overall survival
Estimate the 20-month overall survival rate in patients who cease and who continue SSA.
Time frame: 20 months
Rates of SSA being recommenced over time
Cumulative percentage of SSA recommencement over time.
Time frame: 20 months
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