Recruiting
Phase 2

Somatostatin Analogues

Sponsor:

Australasian Gastro-Intestinal Trials Group

Code:

NCT06345079

Conditions

Neuroendocrine Tumors

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Cessation of somatostatin analogues

Continuation of somatostatin analogues

Study Details

Brief summary:

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.

Conditions

Neuroendocrine Tumors

Study ID

NCT06345079

Start date

Oct 14, 2024

Status verified date

Aug, 2025

Completion date

Jun, 2028

Anticipated

Primary completion date

Sep, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

78 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Continue SSA

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.

experimental: Cease SSA

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.

Interventions

Cessation of somatostatin analogues

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.

Continuation 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.

Primary outcome measure

  • 20-month progression free survival rate after PRRT [ Time Frame: 20 months ]
  • Assess the barriers which would impede the feasibility of a subsequent phase 3 trial [ Time Frame: 20 months ]

Central Contacts and Locations

Central contacts

Julia Kuszewski

+61 02 7208 2725agitg_stopnet_mailbox@gicancer.org.au

Locations

BC Cancer Agency, Vancouver Cancer Centre

Recruiting

Vancouver, British Columbia, Canada, V5Z 4E6

Contacts

Dr Jon Loree

604-877-6000jloree@ctg.queensu.ca

Tathiana Ruiz

tathiana.ruiz@bccancer.bc.ca

Principal Investigator:

Dr Jon Loree

London Health Sciences Centre Research Institute (LHSCRI)

Recruiting

London, Ontario, Canada, N6A 5W9

Contacts

Dr David Laidley

519-685-8500David.Laidley@lhsc.on.ca

Alisha Moynahan

519-685-8500alisha.moynahan@lhsc.on.ca

Principal Investigator:

Dr David Laidley

Ottawa Hospital Research Institute

Recruiting

Ottawa, Ontario, Canada, K1Y 1J8

Contacts

Dr Rachel Goodwin

613-737-8899rgoodwin@toh.ca

Principal Investigator:

Dr Rachel Goodwin

Odette Cancer Centre Sunnybrook Health Sciences Centre

Recruiting

Toronto, Ontario, Canada, TG 260

Contacts

Dr Sten Myrehaug

416-480-4834sten.myrehaug@sunnybrook.ca

Principal Investigator:

Dr Sten Myrehaug

Allan Blair Cancer Centre

Recruiting

Regina, Saskatchewan, Canada, S4T 7T1

Contacts

Dr Mussawar Iqbal

306-766-2213mussawar.iqbal@saskcancer.ca

Principal Investigator:

Dr Mussawar Iqbal

Saskatoon Cancer Centre

Recruiting

Saskatoon, Saskatchewan, Canada, S7N 4H

Contacts

Dr Mita Manna

306-655-2640mita.manna@saskcancer.ca

Principal Investigator:

Dr Mita Manna

More Information

Sponsor

Australasian Gastro-Intestinal Trials Group

Last update posted

Aug 14, 2025

Last verified

Aug, 2025

Keywords

  • Advanced
  • Unresectable grade 1 or 2
  • mid, hind- gut or pancreatic neuroendocrine tumours

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Australasian Gastro-Intestinal Trials Group on 2025-08-14.