Stopping somatostatin analogues after targeted radiotherapy for neuroendocrine tumors

Inclusion Criteria:

* 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.
* Uptake on SSTR PET scan demonstrating somatostatin receptor expression that is suitable for PRRT as judged by the clinical team. FDG PET scans are to be done at the judgement of the treating team and are not required for enrolment into this study.
* PRRT is deemed the most appropriate next treatment step (i.e., patient is inoperable, and liver directed therapies are not preferred)
* ECOG performance status 0 -2
* Written informed consent. Patients must be willing to either cease or continue SSA, depending on which study arm they are randomised to. Patients must be willing to comply with all other study requirements
* Adequate renal, hepatic and haematologic function as judged by the treating team
* Life expectancy of at least 12 months
* Availability of tissue from resection or biopsy samples is desired but is not mandatory for study inclusion. Tissues will only be retrieved if the patient consents to optional translational research sample collection. Similarly, bloods for research purposes will only be collected from those patients who consent to optional translational research sample collection.
* Non-functioning NET: SSA treatment will have been commenced for control of tumour growth and not for carcinoid or other hormone overproduction syndrome, as judged by the clinician and/or NET MDT. Non-functioning NET is judged by the treating clinical team based on patient symptomatology. In addition, for this study, non-functioning tumour is defined as:

  * 24-hour urine 5-hydroxyindoleacetic acid (5HIAA) of \<1.5x upper limit of normal (applies to mid and hind gut patients only).
  * Please note: routine measurement of gastrin, insulin, C-peptide levels, glucagon etc. is not required unless clinically indicated.
  * Never had escalation of the SSA treatment dose to control carcinoid carcinoid or other hormone-related symptoms
  * Never required short acting SSA treatment to control carcinoid carcinoid or other hormone-related symptoms
  * No significant carcinoid induced valvular heart disease IE: Echocardiogram to be done in all patients within 26 weeks of study enrolment and deemed safe to proceed with PRRT by the treating team.

Exclusion Criteria:

* 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.
* Pregnancy. For female patients of childbearing potential and male patients with a female partner who is of childbearing potential, contraception and counselling is required.
* Prior PRRT. Patients being considered for re-treatment with PRRT are not eligible
* Uncontrolled central nervous system metastases. Patients must have completed any surgery or radiation at least 4 weeks prior to registration and must be off corticosteroids for at least 2 weeks
* Any patient, in the opinion of the investigator, who will not comply with study assessments and follow up visits. These might include any social, psychological, or geographical concerns, including alcohol/drug abuse
* Any poorly controlled concurrent medical illness that may prevent the patient from complying with study assessments and follow up. This is to be judged by the treating team
* Any concurrent or prior malignancy that, in the opinion of the treating team, may interfere with study assessments and endpoints