Informations générales (source: ClinicalTrials.gov)
Efficacy, Safety and Patient-reported Outcomes of Peptide Receptor Radionuclide Therapy with 177Lu-edotreotide Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus.
Interventional
Phase 3
Grupo Espanol de Tumores Neuroendocrinos (Voir sur ClinicalTrials)
octobre 2023
juillet 2028
14 août 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Eric BAUDIN | 01/07/2024 14:59:27 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Hospitalier Universitaire (CHU) Bordeux - 33000 - Bourdeaux - France | A responsible person Designated by the Sponsor | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire de Nantes - 44000 - Nantes - France | A responsible person Designated by the Sponsor | Contact (sur clinicalTrials) | |||
| Department of Digestive Oncology - IUCT Rangueil-Larrey, CHU de Toulouse, Toulouse, France - 31100 - Toulouse - France | A responsible person Designated by the Sponsor | Contact (sur clinicalTrials) | |||
| Department of Digestive Oncology, CHU Saint Eloi, Montpellier, France/ ICM Cancer Institute at Montpellier - 34090 - Montpellier - France | A responsible person Designated by the Sponsor | Contact (sur clinicalTrials) | |||
| Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, France - 13005 - Marseille - France | A responsible person Designated by the Sponsor | Contact (sur clinicalTrials) | |||
| Hôpital Edouard Herriot, Lyon - 69003 - Lyon - France | A responsible person Designated by the Sponsor | Contact (sur clinicalTrials) | |||
| Hospital Center University Dijon Bourgogne (CHU Bourgogne) - 21079 - Dijon - France | A responsible person Designed by the sponsor | Contact (sur clinicalTrials) | |||
| Lille University Hospital - 59000 - Lille - France | A responsible person Designated by the Sponsor | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
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.
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.