Comparing Adjuvant Treatment With 177Lu-DOTATATE to Best Supportive Care in Patients After Resection of Neuroendocrine Liver Metastases (NELMAS)

An International Multi-centre, Stratified, Open, Randomized, Comparator-controlled, Parallel-group 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, stratified, open, randomized, comparator-controlled, parallel-group phase II study comparing adjuvant treatment with 177Lu-DOTATATE to best supportive care in patients after resection of neuroendocrine liver metastases.

Study Overview

• Status: Not yet recruiting
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: Lutathera

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chynna Pascual; Phone Number: 02033133170; Email: nelmas-trial@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent prior to any study related procedures
2. Patients aged 18 years or older
3. ECOG / WHO performance status 0 or 1
4. 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
5. 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
6. Patients with a primary tumour already resected or in whom the primary tumour has been resected synchronously with liver metastases
7. 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)
8. 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)

Exclusion Criteria:

1. Less than 4 weeks post-surgery, or any other medical treatment, including chemotherapy, radiotherapy, and intrahepatic therapy
2. High grade neuroendocrine tumours (G3 NET, or neuroendocrine carcinoma [NEC])
3. After R2 (tumour debulking, macroscopically incomplete resection) resection of neuroendocrine liver metastases
4. Patients with non-resectable neuroendocrine liver metastases and/or non-resectable primary tumour and /or non-resectable perihilar lymph node metastases
5. Pregnancy
6. 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)
7. Patients who have received prior systemic and/or liver-directed treatment for their metastatic NET other than somatostatin analogues
8. Hb concentration <5.0 mmol/L (<8.0 g/dL)
9. WBC <2x109/L (2000/mm3)
10. Platelets <75x109/L (75x103/mm3).
11. Total bilirubin >3 x ULN.
12. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
13. Uncontrolled congestive heart failure (NYHA II, III, IV).
14. Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
15. Prior external beam radiation therapy to more than 25% of the bone marrow.
16. Kidney failure with serum creatinine >150 µmol/L (>1.7 mg/dL)
17. Known hypersensitivity to somatostatin analogues

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; Control arm as per standard of care patients go on routine follow up post surgery.
Experimental: Treatment; Treatment with Lutathera post surgery.	Drug: Lutathera; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 years

Collaborators and Investigators

• Sponsor: Imperial College London

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: August 9, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Lutetium Lu 177 dotatate
• Other Study ID Numbers: AF-ICL 01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No