Neuroendocrine Tumor G1 (NET G1)/CarcinoidPhase 2NELMASNCT05987176
Comparison of Adjuvant Treatment With 177Lu-DOTATATE to Best Supportive Care in Patients After Resection of Neuroendocrine Liver Metastases
A Phase 2 study testing Lutathera in people with Neuroendocrine Tumor G1 (NET G1)/Carcinoid and Neuroendocrine Tumor Grade 2, run by Imperial College London at 1 site in United Kingdom.
Trial summary
An international multi-centre, open, randomised, parallel-group phase II study comparing adjuvant treatment with 177Lu-DOTATATE to best supportive care in patients after complete surgical removal of neuroendocrine liver metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumor G1 (NET G1)/Carcinoid, Neuroendocrine Tumor Grade 2, Neuroendocrine Tumors
- What is being tested?
- Lutathera
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Aug 2024to 21 Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent prior to any study related procedures
- Patients aged 18 years or older
- ECOG / WHO performance status 0 or 1
- Patients with well differentiated grade 1 or grade 2 (Ki67<20%) GEP NET confirmed by histological criteria with the primary localisation in stomach, pancreas, or gut
- Patients after R0 (complete macroscopic and microscopic resection) or R1 (complete macroscopic resection, microscopically positive resection margins) resection of neuroendocrine liver metastases confirmed by histological criteria
- Patients with a primary tumour already resected or in whom the primary tumour has been resected synchronously with liver metastases
- MRI scan prior to surgery (within 4 -6 weeks) confirming liver metastases and no extrahepatic disease (except resectable perihilar lymph node involvement and/or primary tumour, if still in place)
- Somatostatin receptor-based imaging (68Ga DOTA-TATE PET/CT prior to surgery (within 12 weeks) confirming liver metastases and no extrahepatic disease (except resectable perihilar lymph node involvement and/or primary tumour, if still in place)
Who cannot join
- Less than 4 weeks post-surgery, or any other medical treatment, including chemotherapy, radiotherapy, and intrahepatic therapy
- High grade neuroendocrine tumours (G3 NET, or neuroendocrine carcinoma [NEC])
- After R2 (tumour debulking, macroscopically incomplete resection) resection of neuroendocrine liver metastases
- Patients with non-resectable neuroendocrine liver metastases and/or non-resectable primary tumour and /or non-resectable perihilar lymph node metastases
- Pregnancy
- Subjects of childbearing potential (both male and female participants) not willing to use a combination of adequate contraceptive measures, e.g., oral contraceptives, IUD, barrier methods of contraception (condom or occlusive cap with spermicide)
Show all 17Show fewer
- Patients who have received prior systemic and/or liver-directed treatment for their metastatic NET other than somatostatin analogues
- Hb concentration <5.0 mmol/L (<8.0 g/dL)
- WBC <2x109/L (2000/mm3)
- Platelets <75x109/L (75x103/mm3).
- Total bilirubin >3 x ULN.
- Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
- Uncontrolled congestive heart failure (NYHA II, III, IV).
- Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
- Prior external beam radiation therapy to more than 25% of the bone marrow.
- Kidney failure with serum creatinine >150 µmol/L (>1.7 mg/dL)
- Known hypersensitivity to somatostatin analogues
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W12 0HS
About this study
Official title: An International Multicentre Randomized Unblinded Phase II Study Comparing Adjuvant Treatment With 177Lu-DOTATATE (Lutathera®) to Best Supportive Care in Patients After Resection of Neuroendocrine Liver Metastases
An international multi-centre, open, randomised, parallel-group phase II study comparing adjuvant treatment with 177Lu-DOTATATE to best supportive care in patients after complete surgical removal of neuroendocrine liver metastases.
In this study, adjuvant treatment with 177Lu-DOTATATE will be compared with best supportive care in patients with well differentiated grade 1 or 2 neuroendocrine tumours in the stomach, pancreas or gut (gastro-entero-pancreatic NETs) who had their primary tumour already removed or in whom both primary and liver tumour metastases removal will take place simultaneously, including removal of perihilar lymph nodes will be eligible.
Read more
The primary objective is to compare overall disease-free survival at 3 years after treatment with 177Lu-DOTATATE to best supportive care between both treatment arms, with equal chances of entering either arm (1:1)
Secondary objectives are to describe and compare the difference in disease-free survival in the liver, overall survival, time to the next anticancer treatment, the cost effectiveness and health-related quality of life. The safety and toxicity of 177Lu-DOTATATE as adjuvant therapy will also be described.
Additionally, the clinical use of blood and urine analysis test (NETest) will be evaluated to identify microscopic remaining disease and detect early the return of the tumour.
Read the detailed description
There will be 2 arms: arm A consisting of best supportive care and arm B, the experimental treatment. Randomisation will be 1:1 as soon as possible after the liver surgery.
The control arm will consist of standard of care. The study will be embedded within the regular clinical pathway for treatment and follow-up of patients with resectable NE LM. The follow-up will be according to current guidelines (e.g., Guidelines of the European Neuroendocrine Tumor Society for the management of advanced intestinal NET and pancreatic NET with locoregional and/or distant metastases). Patients will be followed up in the study for 3 years according to standard post-surgical follow-up protocol and thereafter in their local institution life-long according to follow-up after liver resection for NE LM.
In the treatment arm 177Lu-DOTATATE will be applied. The first cycle will be applied 6±2 weeks after liver resection. The frequency of administration will be 2 cycles (8±1weeks between each cycle). The rationale for 2 cycles in the adjuvant setting instead of 4 (as per standard protocol in palliative setting), assumes that after the removal of the primary tumour and the liver metastases, there will be no macroscopic residual tumour. Thus, the treatment dose should be sufficient to target microscopic disease and have the smallest possible effect on healthy tissue.
In the treatment arm, the patients will have 10 study visits for post -PRRT monitoring (blood tests and clinical assessments). Patients in the standard of care arm will have visits every 3 months. In both arms, patients will have one screening visit and one end of study visit. They will complete QoL questionnaires at baseline and at follow-up visits at 12, 24, and 36 months and bloods/urine will be collected for translational research prior to surgery (while in hospital) and at 6, 12, and 36 months.
Signature of informed consent precedes all study-specific assessments. All patients will have a fresh tumour sample collected during the liver surgery. Disease recurrence will be measured in all patients using liver MRIs every 3 months for the first year and every 6 months for the second to third year and 68Ga DOTA-TATE PET CT every 12 months for 3 years. Any patient with disease recurrence ceases treatment and assessments and will proceed to standard of care treatment for recurrent liver metastases.
Follow-up data will be collected for 5 years overall from the date of randomisation of the last patient.
- Conditions
- Neuroendocrine Tumor G1 (NET G1)/Carcinoid, Neuroendocrine Tumor Grade 2, Neuroendocrine Tumors, Liver Metastases, Gastroenteropancreatic Neuroendocrine Tumor, Gastroenteropancreatic Neuroendocrine Neoplasm
- Being tested
- Lutathera
- Keywords
- NETs, NECs, GEP-NETs, NELMAS, adjuvant, liver metastases
- Medical subject headings
- Neuroendocrine Tumors, Gastro-enteropancreatic neuroendocrine tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LutatheraDrug
Dosage:
In total 14.8 GBq (400 mCi) 177Lu-DOTATATE administered in two equally divided doses. Each dose to be infused over 30 minutes.
Duration of treatment:
Two administrations of 177Lu-DOTATATE (each treatment 7.4 GBQ (200 mCi) at 8±1-week intervals, which can be extended to 16 weeks for resolving acute toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care - Arm A | No intervention | Control arm as per standard of care patients go on routine follow up post surgery. The control arm will consist of best supportive care. The study will be embedded within the regular clinical pathway for treatment and follow-up of patients with resectable NE LM. The follow-up will be according to current guidelines (e.g., Guidelines of the European Neuroendocrine Tumor Society for the management of advanced intestinal NET and pancreatic NET with locoregional and/or distant metastases). Patients will be followed up in the study for 3 years according to standard post-surgical follow-up protocol and thereafter in their local institution life-long according to follow-up after liver resection for NE LM |
| Treatment - Arm B | Experimental | Treatment with Lutathera post surgery.
In the treatment arm 177Lu-DOTATATE will be applied. The frequency of administration will be 2 cycles (8±1weeks between each cycle). The rationale for 2 cycles instead of 4 (as per standard protocol in palliative setting), assumes that there will be no macroscopic residual tumour after liver resection. Thus, the treatment dose should be sufficient to target microscopic disease, and at the same time have smallest possible effect on healthy tissue. Receives: Drug: Lutathera |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival
To compare overall Disease-Free Survival (DFS) at 3 years after treatment with 177Lu-DOTATATE to best supportive care in patients with R0/R1 resected liver metastases of well differentiated (grade 1 or 2) GEP NET and no extrahepatic disease manifestation prior to randomization in the study.
Measured: 3 years
Secondary outcomes (8)
Comparison of Disease free survival in the liver between arm
To compare the Disease-Free Survival (DFS) in the liver between the two study arms
Measured: 3 years
Overall survival
To compare the overall survival (OS) in the liver between the two study arms
Measured: 5 years
Time to tumour recurrence
To compare the Time to Tumour Recurrence (TTR) between the two study arms
Measured: 5 years
Comparison Time to next antineoplastic therapy
To compare the time to administration of subsequent antineoplastic therapy between the two arms
Measured: 5 years
Safety and tolerability of 177Lu-DOTATATE (AEs/SAEs/SUSARs)
To evaluate the safety and tolerability of 177Lu-DOTATATE
Measured: 5 years
Evaluation of quality of life
To evaluate the health-related Quality of Life (QoL) as measured by the EORTC QLQ-C30, QLQ-GI NET 2.1 and EQ-5D questionnaires
Measured: 3 years
Evaluation of self reported health perceptions
To evaluate patient reported outcomes (PROs) as measured by the Short Form-36® (SF-36) Health Survey
Measured: 3 years
Cost-effectiveness evaluation
To evaluate the cost effectiveness assessed by EuroQol-5D (cost for subsequent therapy)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start2 Aug 2024
- Primary completion21 Oct 2025
- Study completion21 Oct 2025
Why it stopped: The study has closed earlier than planned due to one of the funders decision to withdraw the financial support for the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine Tumor G1 (NET G1)/CarcinoidStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- The Taylor Family 2010 Charitable Trust, Novartis/AAA
- Responsible party
- Sponsor
- Investigators
- Andrea Frilling, Prof, Study chair, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05987176
- Sponsor's protocol ID
- AF-ICL 01
- Other IDs
- 2022-003575-42
- Acronym
- NELMAS
- Status last verified
- Jan 2026
- First submitted
- 8 Mar 2023
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International Multicentre Randomized Unblinded Phase II Study Comparing Adjuvant Treatment With 177Lu-DOTATATE (Lutathera®) to Best Supportive Care in Patients After Resection of Neuroendocrine Liver Metastases
- ClinicalTrials.gov ID
- NCT05987176
- Acronym / sponsor ID
- NELMAS / AF-ICL 01
- Conditions
- Neuroendocrine Tumor G1 (NET G1)/Carcinoid, Neuroendocrine Tumor Grade 2, Neuroendocrine Tumors, Liver Metastases, Gastroenteropancreatic Neuroendocrine Tumor, Gastroenteropancreatic Neuroendocrine Neoplasm
- Keywords
- NETs, NECs, GEP-NETs, NELMAS, adjuvant, liver metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study has closed earlier than planned due to one of the funders decision to withdraw the financial support for the study.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- The Taylor Family 2010 Charitable Trust, Novartis/AAA
- Study start
- 2 Aug 2024 (actual)
- Primary completion
- 21 Oct 2025 (actual)
- Study completion
- 21 Oct 2025 (actual)
- First posted
- 14 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An international multi-centre, open, randomised, parallel-group phase II study comparing adjuvant treatment with 177Lu-DOTATATE to best supportive care in patients after complete surgical removal of neuroendocrine liver metastases.
In this study, adjuvant treatment with 177Lu-DOTATATE will be compared with best supportive care in patients with well differentiated grade 1 or 2 neuroendocrine tumours in the stomach, pancreas or gut (gastro-entero-pancreatic NETs) who had their primary tumour already removed or in whom both primary and liver tumour metastases removal will take place simultaneously, including removal of perihilar lymph nodes will be eligible.
The primary objective is to compare overall disease-free survival at 3 years after treatment with 177Lu-DOTATATE to best supportive care between both treatment arms, with equal chances of entering either arm (1:1)
Secondary objectives are to describe and compare the difference in disease-free survival in the liver, overall survival, time to the next anticancer treatment, the cost effectiveness and health-related quality of life. The safety and toxicity of 177Lu-DOTATATE as adjuvant therapy will also be described.
Additionally, the clinical use of blood and urine analysis test (NETest) will be evaluated to identify microscopic remaining disease and detect early the return of the tumour.
Detailed description
There will be 2 arms: arm A consisting of best supportive care and arm B, the experimental treatment. Randomisation will be 1:1 as soon as possible after the liver surgery.
The control arm will consist of standard of care. The study will be embedded within the regular clinical pathway for treatment and follow-up of patients with resectable NE LM. The follow-up will be according to current guidelines (e.g., Guidelines of the European Neuroendocrine Tumor Society for the management of advanced intestinal NET and pancreatic NET with locoregional and/or distant metastases). Patients will be followed up in the study for 3 years according to standard post-surgical follow-up protocol and thereafter in their local institution life-long according to follow-up after liver resection for NE LM.
In the treatment arm 177Lu-DOTATATE will be applied. The first cycle will be applied 6±2 weeks after liver resection. The frequency of administration will be 2 cycles (8±1weeks between each cycle). The rationale for 2 cycles in the adjuvant setting instead of 4 (as per standard protocol in palliative setting), assumes that after the removal of the primary tumour and the liver metastases, there will be no macroscopic residual tumour. Thus, the treatment dose should be sufficient to target microscopic disease and have the smallest possible effect on healthy tissue.
In the treatment arm, the patients will have 10 study visits for post -PRRT monitoring (blood tests and clinical assessments). Patients in the standard of care arm will have visits every 3 months. In both arms, patients will have one screening visit and one end of study visit. They will complete QoL questionnaires at baseline and at follow-up visits at 12, 24, and 36 months and bloods/urine will be collected for translational research prior to surgery (while in hospital) and at 6, 12, and 36 months.
Signature of informed consent precedes all study-specific assessments. All patients will have a fresh tumour sample collected during the liver surgery. Disease recurrence will be measured in all patients using liver MRIs every 3 months for the first year and every 6 months for the second to third year and 68Ga DOTA-TATE PET CT every 12 months for 3 years. Any patient with disease recurrence ceases treatment and assessments and will proceed to standard of care treatment for recurrent liver metastases.
Follow-up data will be collected for 5 years overall from the date of randomisation of the last patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care - Arm A | No intervention | –Control arm as per standard of care patients go on routine follow up post surgery. The control arm will consist of best supportive care. The study will be embedded within the regular clinical pathway for treatment and follow-up of patients with resectable NE LM. The follow-up will be according to current guidelines (e.g., Guidelines of the European Neuroendocrine Tumor Society for the management of advanced intestinal NET and pancreatic NET with locoregional and/or distant metastases). Patients will be followed up in the study for 3 years according to standard post-surgical follow-up protocol and thereafter in their local institution life-long according to follow-up after liver resection for NE LM |
| Treatment - Arm B | Experimental | Drug: LutatheraTreatment with Lutathera post surgery. In the treatment arm 177Lu-DOTATATE will be applied. The frequency of administration will be 2 cycles (8±1weeks between each cycle). The rationale for 2 cycles instead of 4 (as per standard protocol in palliative setting), assumes that there will be no macroscopic residual tumour after liver resection. Thus, the treatment dose should be sufficient to target microscopic disease, and at the same time have smallest possible effect on healthy tissue. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent prior to any study related procedures
- Patients aged 18 years or older
- ECOG / WHO performance status 0 or 1
- Patients with well differentiated grade 1 or grade 2 (Ki67<20%) GEP NET confirmed by histological criteria with the primary localisation in stomach, pancreas, or gut
- Patients after R0 (complete macroscopic and microscopic resection) or R1 (complete macroscopic resection, microscopically positive resection margins) resection of neuroendocrine liver metastases confirmed by histological criteria
Key exclusion criteria (17 listed)
- Less than 4 weeks post-surgery, or any other medical treatment, including chemotherapy, radiotherapy, and intrahepatic therapy
- High grade neuroendocrine tumours (G3 NET, or neuroendocrine carcinoma [NEC])
- After R2 (tumour debulking, macroscopically incomplete resection) resection of neuroendocrine liver metastases
- Patients with non-resectable neuroendocrine liver metastases and/or non-resectable primary tumour and /or non-resectable perihilar lymph node metastases
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LutatheraDosage: In total 14.8 GBq (400 mCi) 177Lu-DOTATATE administered in two equally divided doses. Each dose to be infused over 30 minutes. Duration of treatment: Two administrations of 177Lu-DOTATATE (each treatment 7.4 GBQ (200 mCi) at 8±1-week intervals, which can be extended to 16 weeks for resolving acute toxicity. | Drug | Treatment - Arm B |
Primary outcome
Disease free survival
Time frame: 3 years
To compare overall Disease-Free Survival (DFS) at 3 years after treatment with 177Lu-DOTATATE to best supportive care in patients with R0/R1 resected liver metastases of well differentiated (grade 1 or 2) GEP NET and no extrahepatic disease manifestation prior to randomization in the study.
8 secondary outcomes
Comparison of Disease free survival in the liver between arm
Time frame: 3 years
Overall survival
Time frame: 5 years
Time to tumour recurrence
Time frame: 5 years
Comparison Time to next antineoplastic therapy
Time frame: 5 years
Safety and tolerability of 177Lu-DOTATATE (AEs/SAEs/SUSARs)
Time frame: 5 years
Evaluation of quality of life
Time frame: 3 years
Evaluation of self reported health perceptions
Time frame: 3 years
Cost-effectiveness evaluation
Time frame: 5 years
Results and safety
The study was stopped early (reason given: The study has closed earlier than planned due to one of the funders decision to withdraw the financial support for the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Frilling, Prof study chair
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lutathera in people with Neuroendocrine Tumor G1 (NET G1)/Carcinoid and Neuroendocrine Tumor Grade 2, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study has closed earlier than planned due to one of the funders decision to withdraw the financial support for the study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free survival (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.