Trial Title:
Cessation of Somatostatin Analogues After PRRT in Mid, Hind-Gut and Pancreatic Neuroendocrine Tumours
NCT ID:
NCT06345079
Condition:
Neuroendocrine Tumors
Conditions: Official terms:
Neuroendocrine Tumors
Adenoma, Islet Cell
Somatostatin
Conditions: Keywords:
Advanced
Unresectable grade 1 or 2
mid, hind- gut or pancreatic neuroendocrine tumours
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cessation of somatostatin analogues
Description:
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.
Arm group label:
Cease SSA
Other name:
SSA cessation
Intervention type:
Drug
Intervention name:
Continuation of somatostatin analogues
Description:
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.
Arm group label:
Continue SSA
Other name:
SSA continuation
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Royal Brisbane and Womens Hospital
Address:
City:
Brisbane
Zip:
4006
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Dr Matthew Burge
Phone:
+61 07 3636 8111
Email:
Matthew.Burge@health.qld.gov.au
Contact backup:
Last name:
Poppy Sharman
Phone:
+61 (07) 3647 0865
Email:
Poppy.sharman@health.qld.gov.au
Contact backup:
Last name:
Dr Matthew Burge
Start date:
September 9, 2024
Completion date:
June 2028
Lead sponsor:
Agency:
Australasian Gastro-Intestinal Trials Group
Agency class:
Other
Collaborator:
Agency:
Canadian Cancer Trials Group
Agency class:
Other
Source:
Australasian Gastro-Intestinal Trials Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06345079
