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

NCT03049189 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: ITM-LET-01
• Study Type: interventional
• Target: 309
• Locations: 13 countries
• Sites: 48

Brief 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).

Conditions

Neuroendocrine Tumors

Keywords

non-functional and functional P-NET; non-functional GE-NET

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS)

  PFS will be assessed individually per patient from date of randomization until the date of first documented progression or death, 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 Outcomes (2)

• objective response rates (ORR)

  12 weeks +/- 14 days, up to 30 months

• overall survival (OS)

  12 weeks +/- 14 days, up to 90 months

Study Arms (2)

177Lu-edotreotide PRRT

EXPERIMENTAL

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; Other: Amino-Acid Solution

Everolimus

ACTIVE COMPARATOR

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

Interventions

177Lu-edotreotide PRRT DRUG

PRRT using 177Lu-edotreotide will be performed 3-monthly. A maximum of four cycles will be administered.

Also known as: 177Lu-DOTATOC, 177Lu-Edo

177Lu-edotreotide PRRT

Everolimus DRUG

Everolimus will be administered as a standard dosis of 10 mg daily which may be reduced where required for acceptable tolerability.

Also known as: Afinitor

Everolimus

Amino-Acid Solution OTHER

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

Also known as: Arginine-Lysine Solution

177Lu-edotreotide PRRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.).

Sponsors & Collaborators

• ITM Solucin GmbH: lead
• ABX CRO: collaborator
• PSI CRO: collaborator

Study Sites (52)

Banner Health d.b.a. Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Excel Diagnostics & Nuclear Oncology Center

Houston, Texas, 77042, United States

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Olivia Newton-John Cancer & Wellness Centre, Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Allgemeines Krankenhaus Wien

Vienna, 1090, Austria

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, 3000, Belgium

Location

University Hospital Olomouc

Olomouc, 775 20, Czechia

Location

University Hospital Motol

Prague, 150 06, Czechia

Location

Hospices civils de Lyon

Bron, 69677, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

HP Hôpital Beaujon

Clichy, 92110, France

Location

Institut de Recherche en Cancérologie de Montpellier (IRCM)

Montpellier, 34298, France

Location

CHU de Nantes - Hôtel Dieu

Nantes, 44093, France

Location

IUCT-Oncopole

Toulouse, 31059, France

Location

Zentralklinik Bad Berka GmbH

Bad Berka, 99437, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Universitätsklinikum Bonn

Bonn, 53127, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

University Medical Center, Abteilung für Nuklearmedizin

Hamburg, 20251, Germany

Location

Universitätsklinikum Magdeburg A.ö.R., Otto-von-Guericke Universität

Magdeburg, 39120, Germany

Location

Philipps Universität Marburg

Marburg, 35043, Germany

Location

Klinikum rechts der Isar Technische Universität München

Munich, 81675, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl

Meldola, 47014, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

European Institute of Oncology (EIO)

Milan, 20141, Italy

Location

Academic Medical Center, University of Amsterdam

Amsterdam, 1100DD, Netherlands

Location

MSC Memorial Cancer Centre

Gliwice, 44-100, Poland

Location

"Gammed" Izabela Chuchrowksa

Warsaw, 02-351, Poland

Location

University Cape Town (UCT), Groote Schuur Hospital

Cape Town, 7925, South Africa

Location

University of Pretoria & Steve Biko Academic Hospital

Pretoria, 0001, South Africa

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

ICO Hospitalet, Granvia de l'Hospitalet

Barcelona, 08909, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

University Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Central University Hospital de Asturias (HUCA)

Oviedo, 33011, Spain

Location

University and Polytechnic Hospital La Fe

Valencia, 46026, Spain

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

Inselspital, Universitätsspital Bern

Bern, 3010, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Royal Free NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

177Lu-octreotide, DOTA(0)-Tyr(3)-; Everolimus; amino-acid, glucose, and electrolyte solution

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2017
• First Posted: February 9, 2017
• Study Start: February 2, 2017
• Primary Completion: November 27, 2024
• Study Completion (Estimated): November 1, 2029
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

AU (1); IT (3); US (6); PL (2); ES (6); DE (11); BE (2); ZA (2); NL (1); GB (3); FR (6); CH (3); CZ (2)