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Clinical Trial 19692

Cancer Type: Gastrointestinal Tumor
Interventions:177Lu-edotreotide; everolimus (RAD001)

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Jonathan Strosberg

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Prospective, Randomised, Controlled, Open-label, Multicentre Phase III Study to Evaluate Efficacy and Safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide Compared to Targeted Molecular Therapy with Everolimus in Patients with Inoperable, Progressive, Somato-Statin Receptor-Positive (SSTR+), Neuroendocrine Tumours of Gastroenteric or Pancreatic Origin (GEP-NET).

Summary

The purpose of the study is to evaluate efficacy and safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide compared to targeted molecular therapy with Everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET).

Objective

Primary objective: To demonstrate the efficacy of PRRT with 177Lu-edotreotide to prolong median progression-free survival (mPFS) in patients with inoperable, progressive, SSTR+ GEP-NET, compared to everolimus Secondary objectives; 1. To assess overall survival (OS) during study period, defined as the date from randomisation until death 2. To determine objective response rates (ORR), defined as the proportion of patients achieving partial (PR) or complete response (CR) as best outcome 3. To determine disease control rates (DCR), defined as the proportion of patients achieving stable disease (SD), PR or CR as best outcome 4. To determine the duration of disease control (DDC), measured from the time of initial diagnosis of response (SD, PR or CR), until diagnosis of progression 5. To determine functional response rates (FRR), considering Cg-A and specific hormones (where increased at baseline) 6. To assess the safety and tolerability of 177Lu-edotreotide in GEP-NET patients 7. To determine the health-related quality of life (HRQL) in GEP-NET patients during and after therapy (EORTC QLQ-C30 questionnaire) 8. To evaluate symptomatic tumour response (EORTC GI.NET21 questionnaire) 9. To evaluate the impact of patient characteristics (time from primary diagnosis, time from diagnosis of progression, number of prior therapies (1st vs 2nd line), type of prior therapies, KPS at randomisation) on tumour response 10. To evaluate the impact of tumour histology (histological entity, tumour grade, Ki-67 expression, SSTR expression, functional state) as determined in primary or current bioptic tumour specimen on tumour response Tertiary objectives (in 177Lu-edotreotide patients) 1. To assess differences in tumour and kidney radiation dose estimates, obtained with conventional 2D (planar), compared to hybrid (2D/3D), and 3D (SPECT) imaging 2. To evaluate the value of pre-therapeutic SSTR imaging (SRI) to predict tumour response (globally/at lesion level) 3. To evaluate the relationship between PRRT radiation dose (in Gy) and tumour response (globally/at lesion level)

Inclusion Criteria

  • Histologically and clinically confirmed diagnosis of well-differentiated neuro-endocrine tumour of non-functional gastroenteric origin (GE-NET) or both functional or non-functional pancreatic origin (P-NET)
  • Measurable disease per RECIST 1.1
  • Somatostatin receptor positive (SSTR+) disease
  • Radiological disease progression, defined as progressive disease per RECIST 1.1. criteria

  • Exclusion Criteria

  • Known hypersensitivity to edotreotide or everolimus
  • Known hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus or any other Rapamycin derivative
  • Prior exposure to any peptide receptor radionuclide therapy (PRRT)
  • Prior therapy with mTor inhibitors
  • Prior EFR (external field radiation) to GEP-NET lesions or radioembolisation therapy
  • Therapy with an investigational compound and/or medical device within 30 days prior to randomisation
  • Indication for surgical lesion removal with curative potential
  • Planned alternative therapy (for the period of study participation)
  • Serious non-malignant disease
  • Renal, hepatic, cardiovascular, or haematological organ dysfunction, potentially interfering with the safety of the study treatments
  • Pregnant or breast-feeding women
  • Subjects not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g. persons institutionalised, incarcerated etc.).