Cessation of Somatostatin Analogues After PRRT in Mid, Hind-Gut and Pancreatic Neuroendocrine Tumours

NCT06345079 | Recruiting Phase 2 DMC

• 1 other identifier: AG0219NET
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 12

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  20 months

Secondary Outcomes (9)

• Measure Quality of life using the European Organisation For Research And Treatment Of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30) scales

  20 months

• Measure Quality of life using the EORTC QLQ-GINET21 scales

  20 months

• Cost-effectiveness of SSA therapy cessation

  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

  20 months

• Psycho-oncological impacts of SSA therapy cessation: Fear of Cancer Progression

  20 months

Other Outcomes (1)

• Exploratory analyses

  20 months

Study Arms (2)

Continue SSA

ACTIVE COMPARATOR

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.

Drug: Continuation of somatostatin analogues

Cease SSA

EXPERIMENTAL

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.

Drug: Cessation of somatostatin analogues

Interventions

Cessation of somatostatin analogues DRUG

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.

Also known as: SSA cessation

Cease SSA

Continuation of somatostatin analogues DRUG

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.

Also known as: SSA continuation

Continue SSA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Australasian Gastro-Intestinal Trials Group: lead
• Canadian Cancer Trials Group: collaborator

Study Sites (12)

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

RECRUITING

Wollongong Hospital

Wollongong, New South Wales, 2502, Australia

RECRUITING

Royal Brisbane and Womens Hospital

Brisbane, Queensland, 4006, Australia

RECRUITING

The Queen Elizabeth Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

RECRUITING

BC Cancer Agency, Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

London Health Sciences Centre Research Institute (LHSCRI)

London, Ontario, N6A 5W9, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 1J8, Canada

RECRUITING

Odette Cancer Centre Sunnybrook Health Sciences Centre

Toronto, Ontario, TG 260, Canada

RECRUITING

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

RECRUITING

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H, Canada

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Central Study Contacts

Julia Kuszewski

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2024
• First Posted: April 3, 2024
• Study Start: October 14, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6); CA (6)