The primary objective is to compare the efficacy of lenvatinib plus Best Supportive Care versus Placebo plus Best Supportive Care in the treatment of patients with advanced GIST, after failure of imatinib and sunitinib.
Name: Lenvatinib
Name: Placebo
Name: Best supportive care
Description: PFS, defined as the time from the date of randomisation to the date of the first documented radiological progression (RECIST 1.1) or death due to any cause. PFS will be estimated using the Kaplan-Meier method and will be described in terms of median PFS per arm, and hazard ratio for progression between the 2 arms. Associated 2-sided 95% CI for the estimates will be provided.
Measure: Progression-Free Survival (PFS) Time: Up to 30 monthsDescription: OS, is defined as the time from the date of randomisation until the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
Measure: Overall Survival (OS) Time: Up to 30 monthsDescription: ORR, is the proportion of patients with a Complete Response or Partial Response as Best Overall Response.
Measure: Objective Response Rate (ORR) for patient in the blinded part of the study Time: Up to 30 monthsDescription: BOR, is described as the proportion of patients with a best overall response of Complete Response, Partial Response, Stable Disease or Progressive Disease.
Measure: Best Overall Response (BOR) for patient in the blinded part of the study Time: Up to 30 monthsDescription: QoL, will be assessed using the EORTC QLQ-C30. Scores will be calculated at each time point according to the scoring manuals. Descriptive statistics will be used to evaluate baseline scores and evolution of scores from baseline to each time point. Data will be compared between arms using the Student's t-test.
Measure: Quality of Life (QoL) for patient in the blinded part of the study Time: Up to 30 monthsDescription: The safety will be described mainly on the frequency of adverse events coded using the common toxicity criteria (NCI-CTCAE v5.0) grade. Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment. Adverse events will be coded according to the MedDRA®.
Measure: Patient's tolerance to treatment Time: Up to 30 monthsDescription: OS, is defined as the time from the date of randomisation until the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
Measure: Progression-Free Survival (PFS) In patients from the placebo arm who switched into the active treatment group Time: Up to 30 monthsDescription: Determined by immunohistochemistry (archival formalin fixed paraffin embedded tumor sample)
Measure: Mutation profile : KIT Time: InclusionDescription: Determined by immunohistochemistry (archival formalin fixed paraffin embedded tumor sample)
Measure: Mutation profile: PDGFR Time: InclusionDescription: Trough levels of lenvatinib
Measure: Pharmacokinetic properties of lenvatinib for patient in the blinded part of the study Time: Inclusion, Day 1 of cycles 2, 3, 4, 5, up to 12 months (28 days cycle)Allocation: Randomized
Parallel Assignment
There is one SNP
Patient with a documented mutation in PDGFRA exon 18 (D842V substitution). --- D842V ---