Trial Title:
Efficacy and Safety of Radiotherapy Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus.
NCT ID:
NCT05918302
Condition:
Neuroendocrine Tumors
Lung Neuroendocrine Neoplasm
Thymus Neoplasms
Conditions: Official terms:
Neoplasms
Neuroendocrine Tumors
Lung Neoplasms
Thymus Neoplasms
Thymoma
Everolimus
Edotreotide
Edotreotide lutetium LU-177
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
177Lu-edotreotide
Description:
6 cycles of 7.5 ± 0.7 Giga becquerel (GBq) 177Lu-edotreotide
Arm group label:
Experimental arm
Intervention type:
Drug
Intervention name:
Everolimus
Description:
10 mg orally once daily (QD)
Arm group label:
Control arm
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.
Detailed description:
The LEVEL Trial is a randomized, prospective, international, open-label, phase III study
comparing everolimus and 177Lu-edotreotide in advanced somatostatin receptor positive
(SSTR+) lung and thymic well differentiated neuroendocrine tumors with high expression of
somatostatin receptors confirmed by positron emission tomography somatostatin receptor
imaging.
In the investigator's opinion, patients recruited into the trial must be eligible to
receive everolimus. Patients with both functional and nonfunctional lung and thymus
neuroendocrine tumors (NETs) will be included in this trial. In total, 120 patients will
be randomized in a 3:2 proportion to either experimental or control arms, respectively.
Randomization will be stratified according to prior medical therapy (tumor
treatment-naïve [patients who have not received any prior systemic anticancer therapy]
versus non-treatment- naïve [patients who have received one or two prior line of systemic
anticancer therapy, including somatostatin analogs (SSAs) as anti-tumor treatment]) and
histological differentiation (typical versus atypical / well versus moderately
differentiated). Stratification according to the functional status is not foreseen
considering the poor predictive and prognostic relevance of this criteria on PRRT in the
literature.
Diagnosis of progression and tumor burden will be established based on radiological
information from morphological imaging (magnetic resonance imaging [MRI] and/or computed
tomography [CT]) according to RECIST v1.1. Tumors assessments will be scheduled every 12
± 2 weeks from randomization (the first scan will be performed after Cycle 2 for the
177Lu-edotreotide until radiologically confirmed progression of the disease, initiation
of new subsequent anticancer therapy, or death (whichever comes first). The scanning
modality and protocol should be consistent with the baseline scan. Diagnosis of RECIST
v1.1 progression will be made by the local investigator. The confirmatory scans should be
performed preferably at the next scheduled imaging visit and no less than 4 weeks after
the prior assessment of progression (PD) (in the absence of clinically significant
deterioration). Additional MRI/CT scans may be performed at any other time if, in the
investigator's clinical judgment, PD is suspected. For equivocal findings of progression,
treatment may continue until the next scheduled assessment.
In both arms, for a given patient, trial treatment dosing should be discontinued if there
is evidence of RECIST v1.1 progression, in case of persistent toxicities or if the
patient withdraws consent to continue with treatment. In all cases, if possible, all
other protocol scheduled assessments should be continued until the end of the long-term
follow-up period, unless the patient explicitly withdraws consent to all trial procedures
and follow-up.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written
informed consent.
2. Patients ≥ 18 years of age.
3. 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.
4. 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.
5. 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.
6. Lesions must have shown radiological evidence of disease progression in the 12
months prior to inclusion in the study. Patients who were receiving systemic
anticancer therapy, progression should be documented on therapy or after stopping
therapy due to adverse events or other reasons. Patients without prior therapy,
documentation of progression is also mandatory to watch and wait strategy or during
the follow up after surgery.
7. 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.
8. Patients have radiographically documented and measurable metastatic or locally
advanced disease at baseline according to RECIST v1.1.
9. 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.
10. Patients who have Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1.
11. Adequate organ and bone marrow function based upon meeting all of the following
laboratory criteria:
1. Neutrophil count (ANC) ≥ 1,500/mm^3
2. Platelet count ≥ 75 × 10^9/L
3. Hemoglobin ≥ 8 g/dL
4. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects
with Gilbert's disease or liver metastases
5. Creatinine clearance (CrCl) ≥ 40 mL/min as estimated by the Cockcroft-Gault
formula or as measured by 24-hour urine collection (GFR can also be used
instead of CrCl). Note: renal tract obstruction is not allowed.
6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
or ≤ 5 x ULN for subjects with liver metastases
12. Female subject must provide a negative urine pregnancy test at screening, and must
agree to use a medically accepted and highly effective birth control method (i.e.
those with a failure rate less than 1%) for the duration of the study treatment and
for 6 months after the final dose of study treatment.
13. Female patients must agree not to breastfeed or donate ovules starting at screening
and throughout the study period, and for at least 6 months after the final study
drug administration.
14. Male patients must agree not to donate sperm starting at screening and throughout
the study period, and for at least 6 months after the final study drug
administration.
15. Male patients with a pregnant or breastfeeding partner(s) must agree to abstinence
or use a condom for the duration of the pregnancy or time the partner is
breastfeeding throughout the study period and for at least 6 months after the final
study drug administration.
16. Subject agrees not to participate in another interventional study while on treatment
in the present study.
Exclusion Criteria:
1. Patients who are not able to swallow tablets.
2. 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.
3. Patients with brain mets unless stable on treatment for > 12 weeks and with no
evidence of raised intracranial pressure or mass effect.
4. 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).
5. Patients who have a recent diagnosis of another malignancy (within 12 months prior
to inclusion), patients who are on active treatment for other cancer before the
first dose of study drug, or any evidence of residual disease from a previously
diagnosed malignancy.
6. 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).
7. 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.
8. 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.
9. 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).
10. Prior radiotherapy or major surgery within 12 weeks prior to the first dose of study
drug.
11. 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.
12. Patients who have known hypersensitivity to Everolimus or to any excipient contained
in the drug formulation of Everolimus.
13. 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).
14. Current spontaneous urinary incontinence preventing safe administration of the
investigational medicinal product (IMP), in the investigator's opinion.
15. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Centre Hospitalier Universitaire (CHU) Bordeux
Address:
City:
Bourdeaux
Zip:
33000
Country:
France
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Hospital Center University Dijon Bourgogne (CHU Bourgogne)
Address:
City:
Dijon
Zip:
21079
Country:
France
Status:
Recruiting
Contact:
Last name:
A responsible person Designed by the sponsor
Phone:
934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designed by the sponsor, M.D.
Facility:
Name:
Lille University Hospital
Address:
City:
Lille
Zip:
59000
Country:
France
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Hôpital Edouard Herriot, Lyon
Address:
City:
Lyon
Zip:
69003
Country:
France
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, France
Address:
City:
Marseille
Zip:
13005
Country:
France
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Department of Digestive Oncology, CHU Saint Eloi, Montpellier, France/ ICM Cancer Institute at Montpellier
Address:
City:
Montpellier
Zip:
34090
Country:
France
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Centre Hospitalier Universitaire de Nantes
Address:
City:
Nantes
Zip:
44000
Country:
France
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
I. Gustave Roussy, Paris
Address:
City:
Paris
Zip:
94805
Country:
France
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
Department of Digestive Oncology - IUCT Rangueil-Larrey, CHU de Toulouse, Toulouse, France
Address:
City:
Toulouse
Zip:
31100
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Azienda Ospedaliera Spedali Civili Brescia
Address:
City:
Brescia
Zip:
25123
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - Irsì - Meldola
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
AOU Policlinico G. Martino - Messina
Address:
City:
Messina
Zip:
98124
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Istituto Europeo di Oncologia - Milano
Address:
City:
Milano
Zip:
20141
Country:
Italy
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Istituto Nazionale Tumori IRCCS - Napoli
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Unit of Nuclear Medicine, S. Maria Nuova Hospital-IRCCS of Reggio Emilia, Reggio Emilia, Italy
Address:
City:
Reggio Emilia
Zip:
42123
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence Rome, Rome, Italy.
Address:
City:
Roma
Zip:
00189
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
Azienda Ospedaliera Universitaria Integrata Verona
Address:
City:
Verona
Zip:
37126
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Hospital Universitario Virgen del Rocío
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
Hospital Universitario Central de Asturias
Address:
City:
Oviedo
Zip:
33011
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
ICO Institut Català d'Oncologia L'Hospitalet
Address:
City:
Hospitalet de Llobregat
Zip:
08908
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
Complexo Hospitalario Universitario de Santiago de Compostela
Address:
City:
Santiago De Compostela
Zip:
28042
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Hospital General Universitario Gregorio Marañón
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the Sponsor, M.D.
Facility:
Name:
Hospital Universitario Ramón y Cajal, Madrid
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Status:
Recruiting
Contact:
Last name:
a responsible person Designated by the sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A Responsible person Designated by the Sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Facility:
Name:
Hospital Universitario y Politécnico La Fe
Address:
City:
Valencia
Zip:
46026
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the sponsor
Phone:
+34934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by the sponsor, M.D.
Start date:
October 27, 2023
Completion date:
July 2028
Lead sponsor:
Agency:
Grupo Espanol de Tumores Neuroendocrinos
Agency class:
Other
Collaborator:
Agency:
ITM Oncologics GmbH
Agency class:
Other
Collaborator:
Agency:
MFAR
Agency class:
Other
Source:
Grupo Espanol de Tumores Neuroendocrinos
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05918302
