Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE (COMPOSE)

A Prospective, Randomised, Controlled, Open-label, Multicentre Study to Evaluate Efficacy, Safety and Patient-Reported Outcomes of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-Edotreotide Compared to Best Standard of Care in Patients With Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor-Positive (SSTR+), Neuroendocrine Tumours of GastroEnteric or Pancreatic Origin

The purpose of the study is to evaluate the efficacy, safety & patient-reported outcomes of peptide receptor radionuclide therapy (PRRT) with 177Lu-Edotreotide as 1st or 2nd line of treatment compared to best standard of care in patients with well-differentiated aggressive grade 2 and grade 3, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: 177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT; Other: Amino-Acid Solution; Drug: CAPTEM (Capecitabine and Temozolomide); Drug: Everolimus; Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin)

• Study Type: Interventional
• Enrollment (Actual): 259
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Victoria
    • Melbourne, Victoria, Australia, VIC 3000
      • Peter Maccallum Cancer Centre
• China
  • Shanghai, China, 200000
    • Fudan University Shanghai Cancer Center
  • Wuxi, China, 214122
    • Affiliated Hospital of Jiangnan University
• France
  • Lyon, France, 69003
    • Edouard Herriot Hospital, Medical Oncology Unit
  • Toulouse, France, 31059
    • IUCT Oncopole - Institut Universitaire du Cancer de Toulouse
  • Bordeaux
    • Pessac, Bordeaux, France, 33604
      • Haut-Leveque Hospital, Department of Hepatogastroenterology and Digestive Tract Oncology
  • Cedex
    • Nantes, Cedex, France, 44093
      • Nantes University Hospital Center - Hotel Dieu Hospital
• Germany
  • Berlin, Germany, 13353
    • Charite - University Hospital Berlin
  • Bonn, Germany, 53127
    • University Hospital Bonn, Department of Nuclear Medicine
  • Erlangen, Germany, 91054
    • University Hospital Erlangen, Department of Internal Medicine I - Endocrinology
  • Essen, Germany, 45147
    • University Duisburg-Essen, University Hospital Essen, Clinic for Nuclear Medicine
• India
  • Mumbai, India, 400012
    • Tata Memorial Hospital, Nuclear Medicine & Molecular Imaging
  • Karnataka
    • Bangalore, Karnataka, India, 560027
      • HCG Cancer Centre, Medical Oncology
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • All India Institute Of Medical Sciences, Nuclear Medicine
• Italy
  • Messina, Italy, 98125
    • University Polyclinic Hospital "G. Martino", Department of Biomedical Sciences, Dentistry and Morphological and Functional Imaging, Complex Operational Unit of Nuclear Medicine
  • Milan, Italy, 20141
    • European Institute of Oncology (IEO), IRCCS
  • Rome, Italy, 00168
    • University Polyclinic Foundation "Agostino Gemelli" - IRCCS, Complex Operative Unit of Medical Oncology
• Netherlands
  • Amsterdam, Netherlands, 1081-HV
    • VU Medical Center (VUMC), Department of Medical Oncology
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus University Medical Center Rotterdam
• Spain
  • Barcelona, Spain, 08035
    • University Hospital Vall d'Hebron, Department of Medical Oncology
  • Barcelona, Spain, 199-203
    • ICO Hospitalet, Catalan Institute of Oncology
  • Madrid, Spain, 28007
    • University General Hospital Gregorio Maranon
  • Madrid, Spain, 28041
    • University Hospital 12 de Octubre, Department of Gastroenterology
  • Oviedo, Spain, 33011
    • Central University Hospital de Asturias (HUCA), IUOPA - Universitary Institute of Oncology
  • Santiago de Compostela, Spain, 15706
    • University Hospital Complex of Santiago (CHUS)
  • Valencia, Spain, 46026
    • University and Polytechnic Hospital La Fe, Endocrinology
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital, Nuclear Medicine
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester, Department of Oncology
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University Alvin J. Siteman Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10128
      • ICAHN School of Medicine at Mount Sinai, Tish Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University School of Medicine, Duke Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah, Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged ≥ 18 years.
• Histologically confirmed diagnosis of unresectable, well-differentiated GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs). measurable site of disease per RECIST v1.1 (Response evaluation criteria in solid tumors) using contrast computed tomography (CT) / magnetic resonance imaging (MRI).
• Somatostatin receptor-positive (SSTR+) disease.

Exclusion Criteria:

• Known hypersensitivity to Lutetium 177Lu, edotreotide, DOTA (dodecane tetraacetic acid), any of the comparators, or any excipient or derivative (e.g. rapamycin).
• Prior (Peptide Receptor Radionuclide Therapy) PRRT.
• Any major surgery within 4 weeks prior to randomization in the trial.
• Therapy with an investigational compound and/or medical device within 30 days or 7 half-life periods (whichever is longer) prior to randomization.
• Other known malignancies.
• Serious non-malignant disease.
• Renal, hepatic, cardiovascular, or hematological organ dysfunction, potentially interfering with the safety of the trial treatments.
• Pregnant or breastfeeding women.
• Patients not able to declare meaningful informed consent on their own or any other vulnerable population to that.

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: Peptide Receptor Radionuclide Therapy (PRRT) Arm	Drug: 177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT; Peptide Receptor Radionuclide Therapy (PRRT) using 177Lu-edotreotide with a defined number of 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 lysine and arginine diluted in an electrolyte solution.; Other Names: Arginine-Lysine Solution
Active Comparator: CAPTEM(Capecitabine-Temozolomide), Everolimus, FOLFOX(Folinic acid + Fluorouracil + Oxaliplatin)	Drug: CAPTEM (Capecitabine and Temozolomide); Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.; Drug: Everolimus; Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.; Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin); Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	PFS (Progression-Free Survival), defined as the time from randomization until documented RECIST v1.1 (Response evaluation criteria in solid tumors) progression or death, whichever occurs first.	Every 12 weeks from randomization until disease progression or death whichever occurs earlier, during the time necessary to observe 148 Progression Free Survival (PFS) events.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS (Overall Survival), defined as the time from randomization until death;	Up to 3 years after disease progression, or to a maximum of 5 years after randomization

Collaborators and Investigators

• Sponsor: ITM Solucin GmbH

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2021
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: GastroEnteroPancreatic; non-functional and functional GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NET)
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Gastro-enteropancreatic neuroendocrine tumor; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Nucleic Acids, Nucleotides, and Nucleosides; Dacarbazine; Triazenes; Imidazoles; Enzymes and Coenzymes; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Macrolides; Lactones; Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Deoxyribonucleosides; Sirolimus; Temozolomide; Capecitabine; Oxaliplatin; Everolimus; Fluorouracil; Leucovorin; Folfox protocol; amino-acid, glucose, and electrolyte solution; 177Lu-octreotide, DOTA(0)-Tyr(3)-
• Other Study ID Numbers: DP-1111-02CT

Drug and device information, study documents

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