TheranosticTrials.org

Clinical Trial · NCT05987176

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

Overview

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.

Sponsor

Imperial College London

Phase

Phase 2

Contacts

Andrea Frilling, Prof (STUDY_CHAIR)

ClinicalTrials.gov

NCT05987176

Drug / Compound

DOTATATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: DOTA

DOTATATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: DOTA

Eligibility

Inclusion

  • 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)
  • ECOG / WHO performance status 0 or 1
  • 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)
  • 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

Exclusion

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