Comparison of Adjuvant Treatment With 177Lu-DOTATATE to Best Supportive Care in Patients After Resection of Neuroendocrine Liver Metastases

NCT05987176 | Terminated Phase 2 DMC

• 2 other identifiers: AF-ICL 012022-003575-42
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Neuroendocrine Tumor Grade 2; Neuroendocrine Tumor G1 (NET G1)/Carcinoid; Neuroendocrine Tumors; Liver Metastases; Gastroenteropancreatic Neuroendocrine Tumor; Gastroenteropancreatic Neuroendocrine Neoplasm

Keywords

NETs; NECs; GEP-NETs; NELMAS; adjuvant; liver metastases

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Secondary Outcomes (8)

• Comparison of Disease free survival in the liver between arm

  3 years

• Overall survival

  5 years

• Time to tumour recurrence

  5 years

• Comparison Time to next antineoplastic therapy

  5 years

• Safety and tolerability of 177Lu-DOTATATE (AEs/SAEs/SUSARs)

  5 years

Other Outcomes (1)

• NETest

  3 years

Study Arms (2)

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.

Drug: Lutathera

Interventions

Lutathera DRUG

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.

Treatment - Arm B

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Imperial College London: lead
• The Taylor Family 2010 Charitable Trust: collaborator
• Novartis/AAA: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Gastro-enteropancreatic neuroendocrine tumor

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

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

Study Officials

• Andrea Frilling, Prof

  Imperial College London

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: March 8, 2023
• First Posted: August 14, 2023
• Study Start: August 2, 2024
• Primary Completion: October 21, 2025
• Study Completion: October 21, 2025
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)