Neoplasms

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Rare Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

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Somatostatin

Octreotide

Hormones

Hormone Antagonists

Patients randomised to continue SSA will receive a SSA injection ≥28 days prior to the first PRRT cycle, during PRRT cycle, and every 4 weeks after completion of PRRT.

Patients randomised to cease SSA will receive SSA injection ≥28 days prior to their first cycle of PRRT. Patients will not receive any further long acting SSA injections after this time.

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.

Cessation of somatostatin analogues

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.

Continuation of somatostatin analogues

Laura Carolan

Julia Kuszewski

Matthew Burge

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 and hind-gut 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 or hind gut 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 Hunter Medical Research Institute (HMRI). 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.

Cessation of Somatostatin Analogues After PRRT in Mid-Gut Neuroendocrine Tumours

A Randomised Study of Cessation of Somatostatin Analogues After Peptide Receptor Radionuclide Therapy in Mid-Gut Neuroendocrine Tumours (STOPNET)

Exploratory analyses including, but not limited to: Define and validate NET tissue and circulating biomarkers with a particular focus on miRNA.

Estimate the 20-month progression free survival rate after PRRT in patients who cease and who continue SSA.

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 18-month recruitment period

Responses to the QLQ-C30 scale from 0-100 using EORTC guidelines, with higher scores reflecting better level of functioning.

Responses to the QLQ-GINET21 scale from 0-100 using EORTC guidelines, with higher scores reflecting more severe symptoms.

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 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)

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)

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 to commencement of subsequent therapy (e.g re-challenge with PRRT, liver directed therapies, chemotherapy, targeted therapies)

Estimate the 20-month overall survival rate in patients who cease and who continue SSA.

Cumulative percentage of SSA recommencement over time.

Spots Global Cancer Trial Database for continuation of somatostatin analogues