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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: Lutathera


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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. Kidney failure with serum creatinine >150 µmol/L (>1.7 mg/dL) Known hypersensitivity to somatostatin analogues

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |