Efficacy and Safety of Radiotherapy Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus.

NCT05918302 | Recruiting Phase 3

• 2 other identifiers: GETNE-T22172022-502154-13-00
• Study Type: interventional
• Target: 120
• Locations: 4 countries
• Sites: 27

Brief Summary

LEVEL trial aims to demonstrate the higher efficacy of 177Lu-edotreotide over everolimus in patients with well to moderately differentiated neuroendocrine tumors of the lung and thymus who require systemic therapy. It is hypothesized that 177Lu-edotreotide may significantly increase the progression-free survival (PFS) compared to everolimus in lung and thymic carcinoids.

Conditions

Neuroendocrine Tumors; Lung Neuroendocrine Neoplasm; Thymus Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-free survival (PFS) defined as the time from the date of randomization to the date of first documentation of disease progression according to RECIST 1.1 by investigator-assessment or death due to any cause, whichever occurs first. In the primary analysis, PFS will be censored at the date of the last adequate tumor assessment if no PFS event is observed prior to the analysis cut-off date.

  Throughout the study period, approximately 3 years per patient

Secondary Outcomes (5)

• Objective response rate (ORR)

  Throughout the study period, approximately 3 years per patient

• Disease control rate (DCR)

  Throughout the study period, approximately 3 years per patient

• Duration of response (DoR)

  Throughout the study period, approximately 3 years per patient

• Overall Survival (OS)

  Throughout the study period, approximately 3 years per patient, at each visit. Long-term follow-up to be performed at least every 6 months.

• Patient reported quality of life

  Throughout the study period, approximately 3 years per patient. Assessed every 12 weeks from randomization to progression

Study Arms (2)

Experimental arm

EXPERIMENTAL

Treatment with 6 cycles of 7.5 ± 0.7 GBq 177Lu-edotreotide. The prescribed treatment administration is as follows: a 6 (±2) weeks interval between cycles 1 and 2 followed by all remaining cycles (3-6) given 8 (± 1) weeks after the previous cycle), where possible, or until disease progression, intolerable toxicity or death, whichever occurs first.

Drug: 177Lu-edotreotide

Control arm

ACTIVE COMPARATOR

Everolimus 10 mg orally once daily (QD) until disease progression or intolerable toxicity or death, whichever occurs first.

Drug: Everolimus

Interventions

177Lu-edotreotide DRUG

6 cycles of 7.5 ± 0.7 Giga becquerel (GBq) 177Lu-edotreotide

Experimental arm

Everolimus DRUG

10 mg orally once daily (QD)

Control arm

Eligibility Criteria

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

You may qualify if:

• Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent.
• Patients ≥ 18 years of age.
• Patients who have histologically confirmed metastatic or locally advanced unresectable well/moderately differentiated; World Health Organization (WHO\]) 2015 criteria; neuroendocrine tumor of lung (typical and atypical carcinoids) or thymus origin either functioning or non-functioning.
• Patients must have the appropriate pathological features based on WHO classification, and description of proliferation activity as indicated by mitotic count per 10 high-power fields (HPF) and presence of necrosis, or Ki67 index.
• In SSTR imaging all RECIST v1.1 selected target lesions and all other lesions considered dominant by the investigator should be positive. If an fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) is performed (not mandatory), all FDG-PET positive RECIST v1.1 target lesions and all other FDG-PET positive lesions considered dominant by the investigator should also be positive in SSRT imaging.
• Patients may be included in first-line therapy (systemic treatment naïve) or may have experienced progression on somatostatin analogues or additional systemic treatments, which may include but not limited to chemotherapy, targeted agents or immunotherapy (maximum of 2 prior systemic anti-tumor treatments).
• Note: Somatostatin analogues for patients with functioning tumors are allowed.
• Patients have radiographically documented and measurable metastatic or locally advanced disease at baseline according to RECIST v1.1.
• An archival tumor tissue sample should be available for submission to the central laboratory prior to study treatment (36 months). If an archival tumor tissue sample is not available, a new biopsy tissue sample should be provided if feasible.
• Patients who have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ and bone marrow function based upon meeting all of the following laboratory criteria:
• Neutrophil count (ANC) ≥ 1,500/mm\^3
• Platelet count ≥ 75 × 10\^9/L
• Hemoglobin ≥ 8 g/dL
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease or liver metastases

You may not qualify if:

• Patients who are not able to swallow tablets.
• Patients with poorly-differentiated or high-grade neuroendocrine carcinoma (i.e. large cell neuroendocrine carcinoma of lung, small cell lung cancer) or mixed tumors (i.e. adenocarcinoid tumor) are not eligible.
• Patients with brain mets unless stable on treatment for \> 12 weeks and with no evidence of raised intracranial pressure or mass effect.
• Patients who have ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
• Patients who have a known active Hepatitis B (e.g., HBsAg reactive) or active hepatitis C (e.g., hepatitis C virus (HCV) RNA \[qualitative\] is detected). Patients who have a known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2).
• Patients who have received a live vaccine up to 4 weeks prior to the first dose of trial treatment.
• Note:Live attenuated vaccines should not be administered during the trial treatment and over the next 3 months after the last treatment dose.
• Patients who have documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study drug.
• Prior peptide receptor radionuclide therapy (PRRT) or mammalian target of rapamycin (mTOR) inhibitors (e.g. deforolimus, everolimus, sirolimus, temsirolimus, etc.); or hepatic radio-embolization (within 6 months prior to first dose of study treatment).
• Prior radiotherapy or major surgery within 12 weeks prior to the first dose of study drug.
• Patients who have had chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 4 weeks prior to the first dose of study drug.
• Patients who have known hypersensitivity to Everolimus or to any excipient contained in the drug formulation of Everolimus.
• Patients who have known hypersensitivity to 177Lu-edotreotide or to any excipient contained in the drug formulation of 177Lu-edotreotide or the nephroprotective amino acid solution (AAS).
• Current spontaneous urinary incontinence preventing safe administration of the investigational medicinal product (IMP), in the investigator's opinion.
• Patients who have other underlying medical conditions that, in the opinion of the investigator, would impair the ability of the subject to receive or tolerate the planned treatment and follow-up.

Sponsors & Collaborators

• ITM Oncologics GmbH: collaborator
• MFAR: collaborator
• Grupo Espanol de Tumores Neuroendocrinos: lead

Study Sites (27)

Antwerp University Hospital (UZA)

Edegem, Edegem, 2650, Belgium

RECRUITING

UCL Saint-Luc

Brussels, 1200, Belgium

RECRUITING

CHU Liège

Liège, 4000, Belgium

RECRUITING

Hospital Center University Dijon Bourgogne (CHU Bourgogne)

Dijon, Dijon, 21079, France

RECRUITING

Centre Hospitalier Universitaire (CHU) Bordeux

Bourdeaux, 33000, France

RECRUITING

Lille University Hospital

Lille, 59000, France

RECRUITING

Hôpital Edouard Herriot, Lyon

Lyon, 69003, France

RECRUITING

Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, France

Marseille, 13005, France

RECRUITING

Department of Digestive Oncology, CHU Saint Eloi, Montpellier, France/ ICM Cancer Institute at Montpellier

Montpellier, 34090, France

RECRUITING

Centre Hospitalier Universitaire de Nantes

Nantes, 44000, France

RECRUITING

I. Gustave Roussy, Paris

Paris, 94805, France

RECRUITING

Azienda USL IRCCS Di Reggio Emilia

Reggio Emilia, Reggio Emilia, 42123, Italy

RECRUITING

AOU Consorziale Policlinico di Bari - CROB Referrall Cancer Center of Basilicata

Bari, 70124, Italy

RECRUITING

IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - Irsì - Meldola

Meldola, 47014, Italy

RECRUITING

Istituto Europeo di Oncologia - Milano

Milan, 20141, Italy

RECRUITING

Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence Rome, Rome, Italy.

Roma, 00189, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37126, Italy

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, Andalusia, 41013, Spain

RECRUITING

ICO Institut Català d'Oncologia L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Complexo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, Galicia, 28042, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

RECRUITING

Hospital Universitario Ramón y Cajal, Madrid

Madrid, Madrid, 28034, Spain

RECRUITING

Fundación Jiménez Díaz University Hospital

Madrid, Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46026, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Related Publications (1)

• Capdevila J, Pubul V, Anido U, Walter T, Molina-Cerrillo J, Alonso-Gordoa T, Garcia-Carbonero R, San-Roman-Gil M, Llana B, Jimenez-Fonseca P, Benavent Vinuales M, Ansquer C, Baudin E, Lepage C, Del Olmo-Garcia M, Ruffinelli JC, Beron A, Haissaguerre M, Deshayes E, Taieb D, Baldari S, Sansovini M, Cingarlini S, Filice A, Panzuto F, Alvarez-Alvarez R, Lousberg L, Aboubakar Nana F, Hernando J, Garcia-Alvarez A, Garcia-Burillo A, Villacampa G, Vandamme T, Fazio N, Durand A. A Randomized clinical trial evaluating the impact on survival and quality of life of 177Lutetium[Lu]-edotreotide versus everolimus in patients with neuroendocrine tumors of the lung and thymus: the LEVEL study (GETNE T-2217). BMC Cancer. 2025 Apr 4;25(1):613. doi: 10.1186/s12885-025-13941-3.

  PMID: 40186126 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors; Thymus Neoplasms

Interventions

177Lu-octreotide, DOTA(0)-Tyr(3)-; Everolimus

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Jaume Capdevila, M.D. Ph.D.

  Hospital Vall d'Hebron

  STUDY CHAIR

Central Study Contacts

Federico Nepote

CONTACT

+34934344412; investigacion@mfar.net

Study Design

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

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: June 26, 2023
• Study Start: October 27, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: March 6, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); FR (8); IT (6); ES (10)