Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients (COMPETE)

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, Somatostatin Receptor-positive (SSTR+), Neuroendocrine Tumours of Gastroenteric or Pancreatic Origin (GEP-NET)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: 177Lu-edotreotide PRRT; Other: Amino-Acid Solution; Drug: Everolimus

• Study Type: Interventional
• Enrollment (Actual): 309
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Olivia Newton-John Cancer & Wellness Centre, Austin Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Wien, Austria, 1090
    • Allgemeines Krankenhaus Wien
• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven
• Czechia
  • Olomouc, Czechia, 775 20
    • University Hospital Olomouc
  • Prague, Czechia, 150 06
    • University Hospital Motol
• France
  • Bron, France, 69677
    • Hospices Civils de Lyon
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Clichy, France, 92110
    • HP Hôpital Beaujon
  • Montpellier, France, 34298
    • Institut de Recherche en Cancérologie de Montpellier (IRCM)
  • Nantes, France, 44093
    • CHU de Nantes - Hôtel Dieu
  • Toulouse, France, 31059
    • IUCT-Oncopole
• Germany
  • Bad Berka, Germany, 99437
    • Zentralklinik Bad Berka GmbH
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • Erlangen, Germany, 91054
    • Universitatsklinikum Erlangen
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Hamburg, Germany, 20251
    • University Medical Center, Abteilung für Nuklearmedizin
  • Magdeburg, Germany, 39120
    • Universitätsklinikum Magdeburg A.ö.R., Otto-von-Guericke Universität
  • Marburg, Germany, 35043
    • Philipps Universität Marburg
  • Munich, Germany, 81675
    • Klinikum rechts der Isar Technische Universität München
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm
  • Wurzburg, Germany, 97080
    • Universitätsklinikum Würzburg
• Italy
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano, Italy, 20141
    • European Institute of Oncology (EIO)
• Netherlands
  • Amsterdam, Netherlands, 1100DD
    • Academic Medical Center, University of Amsterdam
• Poland
  • Gliwice, Poland, 44-100
    • MSC Memorial Cancer Centre
  • Warsaw, Poland, 02-351
    • "Gammed" Izabela Chuchrowksa
• South Africa
  • Cape Town, South Africa, 7925
    • University Cape Town (UCT), Groote Schuur Hospital
  • Pretoria, South Africa, 0001
    • University of Pretoria & Steve Biko Academic Hospital
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron University Hospital
  • Barcelona, Spain, 08909
    • ICO Hospitalet, Granvia de l'Hospitalet
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center Madrid
  • Madrid, Spain, 28041
    • University Hospital 12 de Octubre
  • Oviedo, Spain, 33011
    • Central University Hospital de Asturias (HUCA)
  • Valencia, Spain, 46026
    • University and Polytechnic Hospital La fe
• Switzerland
  • Basel, Switzerland, 4031
    • Universitatsspital Basel
  • Bern, Switzerland, 3010
    • Inselspital, Universitätsspital Bern
  • Zürich, Switzerland, 8091
    • Universitatsspital Zurich
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner Health d.b.a. Banner MD Anderson Cancer Center
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Texas
    • Houston, Texas, United States, 77042
      • Excel Diagnostics & Nuclear Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically 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
• Progressive disease based on RECIST 1.1. criteria as evidenced by two morphological imaging examinations made with the same imaging method (either CT or MRI)

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 within 90 days before randomisation 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
• Clinically relevant 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.).

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
Experimental: 177Lu-edotreotide PRRT; 177Lu-edotreotide (177Lu-DOTATOC) A maximum of four cycles of 7.5 ± 0.7 GBq (gigabequerel) 177Lu-edotreotide, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 4 cycles, 90 days apart (total duration: 270 days/9 months)	Drug: 177Lu-edotreotide PRRT; PRRT using 177Lu-edotreotide will be performed 3-monthly. A maximum of four cycles will be administered.; Other Names: 177Lu-DOTATOC; 177Lu-Edo; Other: Amino-Acid Solution; The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of 25 g lysine and 25 g arginine diluted in 2000 mL of electrolyte solution, infused over 4 - 6 h, starting 30 - 60 min before PRRT; Other Names: Arginine-Lysine Solution
Active Comparator: Everolimus; Everolimus (Afinitor ®) Doses: 10 mg/d Route of administration: Oral Duration of treatment: Continuous daily treatment until diagnosis of progression or End of Study (EOS)	Drug: Everolimus; Everolimus will be adminstered as a standard dosis of 10 mg daily which may be reduced where required for acceptable tolerability.; Other Names: Afinitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival (PFS)	PFS will be assessed individually per patient from date of randomization until the date of first documented progression, assessed up to 30 months, primary outcome will be measured by CT/MRI every 12 weeks +/- 14 days	12 weeks +/- 14 days, up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	OS as secondary outcome measure will be assessed per patient from date of randomization until the date of death, whichever came first	every 3 months for a period of at least 30 months

Collaborators and Investigators

• Sponsor: ITM Solucin GmbH
• Collaborators: ABX CRO; PSI CRO

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimated): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: non-functional and functional P-NET; non-functional GE-NET
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Radiopharmaceuticals; Protein Kinase Inhibitors; MTOR Inhibitors; Pharmaceutical Solutions; Everolimus; Edotreotide; Edotreotide lutetium LU-177
• Other Study ID Numbers: ITM-LET-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No