Patients with advanced/metastatic, histologically confirmed, grade 1/2 (G1/G2) of 2010 WHO classification neuroendocrine tumors of the pancreas after progression to a previous targeted agent (cohort A) or gastrointestinal tract after progression to somatostatin analogues (cohort B). MedDRA version: 18.0 Level: LLT Classification code 10062476 Term: Neuroendocrine tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.0 Level:
Conditions
Interventions
Product Name: lenvatinib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lenvatinib
CAS Number: 417716-92-8
Current Sponsor code: na
Other descriptive name: LENVATINIB
Concentration unit: mg m
Sponsors
GETNE (Grupo Español de Tumores Neuroendocrinos)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must have histologically confirmed diagnosis of one of the following advanced/metastatic neuroendocrine tumor types: a) WHO Classification G1/G2 (Ki67=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded from this study: 1. WHO Classification G3 neuroendocrine tumors of the pancreas and gastrointestinal tract. 2. Two or more prior lines of targeted agents-based therapy in pancreatic origin and any previous line of targeted therapy for gastrointestinal origin or any ongoing antiproliferative treatment for advanced/metastatic neuroendocrine tumors, with the exception of somatostatin analogues therapy. 3. More than one previous line of chemotherapy in pancreatic neuroendocrine tumors. 4. Previous chemotherapy in gastrointestinal neuroendocrine tumors. 5. Prior treatment with lenvatinib. 6. Subjects who have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment. This does not apply to the use of somatostatin analogues for symptomatic therapy. 7. Major surgery within 3 weeks prior to the first dose of study drug. 8. Subjects having > 1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ? 1 g/24h will be ineligible. 9. Gastrointestinal malabsorption, or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib. 10. Significant cardiovascular impairment. 11. Prolongation of QTcF interval to > 480 msec. 12. Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. Treatment with low molecular weight heparin (LMWH) is allowed. 13. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug. 14. Active infection (any infection requiring treatment). 15. Active malignancy within the past 5 years. 16. Known intolerance to any of the study drugs (or any of the excipients). 17. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial. 18. Females who are pregnant or breastfeeding. 19. Documented active alcohol or drug abuse. 20. Patients with a prior history of non-compliance with medical regimens.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective To assess the efficacy of lenvatinib on tumor objective response rate in two independent cohorts of patients with advanced neuroendocrine tumors: patients with advanced/metastatic G1/G2 pancreatic neuroendocrine tumors after progression to a previous targeted agent (cohort A), and patients with advanced/metastatic G1/G2 neuroendocrine tumors of gastrointestinal tract after failure to somatostatin analogues therapy (cohort B).;Secondary Objective: Secondary objectives To determine the safety and tolerability of lenvatinib. To estimate the early tumor shrinkage rate and the deepness of response of lenvatinib in each cohort of patients. To estimate progression-free survival in both cohorts of patients. Exploratory objectives To evaluate biochemical response (changes in CgA and NSE levels) and its association with response rate and progression-free survival. To assess whether baseline tumor and blood biomarkers may be predictive of response to lenvatinib. To explore additional hypotheses related to biomarkers and relationship to lenvatinib, neuroendocrine tumors, other endocrine disorders and/or cancer which may arise from internal or external research activities.;Primary end point(s): The primary efficacy endpoint is overall response rate (ORR) by RECIST v1.1 ? ORR is the proportion of subjects who have best overall response of CR or PR.;Timepoint(s) of evaluation of this end point: Data cut-off for the primary study analysis will happen following after the last patient included in the study has performed the second tumor evaluation (week 18 after first dose of study drug as first evaluation will take place 6 weeks after first dose, following tumor assessment will take place every 12 weeks until documentation of disease progression or start of another anticancer therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Progression-free survival (PFS) is defined as the time from the date of randomization to the date of first documentation of disease progression or death (whichever occurs first) using RECIST 1.1. PFS censoring rules will follow FDA guidance in 2007. ? Early tumor shrinkage (ETS) rate defined as 20% reduction in target lesions after the first 6 weeks of treatment (first tumor evaluation) ? Deepness of response (DpR) defined as percentage of maximum tumor shrinkage observed at the nadir compared with baseline.;Timepoint(s) of evaluation of this end point: Data cut-off for the primary study analysis will happen following after the last patient included in the study has performed the second tumor evaluation (week 18 after first dose of study drug as first evaluation will take place 6 weeks after first dose, following tumor assessment will take place every 12 weeks until documentation of disease progression or start of another anticancer therapy | — |
Countries
Spain
Contacts
Public ContactDr. Jaume Capdevila
GETNE (Grupo Español Tumores Neuroendocrinos)
Outcome results
None listed