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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06345079




Registration number
NCT06345079
Ethics application status
Date submitted
14/03/2024
Date registered
3/04/2024
Date last updated
5/06/2024

Titles & IDs
Public title
Cessation of Somatostatin Analogues After PRRT in Mid, Hind-Gut and Pancreatic Neuroendocrine Tumours
Scientific title
A Randomised Study of Cessation of Somatostatin Analogues After Peptide Receptor Radionuclide Therapy in Mid, Hind-Gut and Pancreatic Neuroendocrine Tumours (STOPNET)
Secondary ID [1] 0 0
AG0219NET
Universal Trial Number (UTN)
Trial acronym
STOPNET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroendocrine Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Pancreatic
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cessation of somatostatin analogues
Treatment: Drugs - Continuation of somatostatin analogues

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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
20-month progression free survival rate after PRRT
Timepoint [1] 0 0
20 months
Primary outcome [2] 0 0
Assess the barriers which would impede the feasibility of a subsequent phase 3 trial
Timepoint [2] 0 0
20 months
Secondary outcome [1] 0 0
Measure Quality of life using the European Organisation For Research And Treatment Of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30) scales
Timepoint [1] 0 0
20 months
Secondary outcome [2] 0 0
Measure Quality of life using the EORTC QLQ-GINET21 scales
Timepoint [2] 0 0
20 months
Secondary outcome [3] 0 0
Cost-effectiveness of SSA therapy cessation
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Psycho-oncological impacts of SSA therapy cessation: Decision Regret
Timepoint [4] 0 0
20 months
Secondary outcome [5] 0 0
Psycho-oncological impacts of SSA therapy cessation: Fear of Cancer Progression
Timepoint [5] 0 0
20 months
Secondary outcome [6] 0 0
Psycho-oncological impacts of SSA therapy cessation: Decisional Conflict
Timepoint [6] 0 0
20 months
Secondary outcome [7] 0 0
Time to commencement of subsequent therapy
Timepoint [7] 0 0
20 months
Secondary outcome [8] 0 0
Overall survival
Timepoint [8] 0 0
20 months
Secondary outcome [9] 0 0
Rates of SSA being recommenced over time
Timepoint [9] 0 0
20 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/07/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2028
Actual
Sample size
Target
78
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Royal Brisbane Women's Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Brisbane

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Gastro-Intestinal Trials Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Canadian Cancer Trials Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06345079
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Laura Carolan
Address 0 0
Country 0 0
Phone 0 0
+61 2 7208 2710
Fax 0 0
Email 0 0
agitg_stopnet_mailbox@gicancer.org.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06345079