Patients with locally advanced or metastatic GIST after failure of imatinib and sunitinib (either on 3rd line treatment or beyond a 3rd line with regorafenib)
Conditions
Interventions
Trade Name: Lenvima
Product Code: E7080
Pharmaceutical Form: Capsule
INN or Proposed INN: Lenvatinib
CAS Number: 857890-39-2
Other descriptive name: LENVATINIB MESILATE
Pharmaceutical form of the plac
Sponsors
Centre Léon Bérard
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1. Male or female = 18 years at the day of consenting to the study I2. Patient must have histologically confirmed diagnosis of GIST I3. Disease must be locally advanced or metastatic I4. Patient who failed (disease progression and/or intolerance) previously at least to imatinib and sunitinib. Nota Bene: patients with more than 2 previous anticancer treatments are eligible. I5. Patient must have evidence of measurable disease as per the RECIST version 1.1 (Appendix 2) I6. Patient must have documented disease progression I7. ECOG performance status 0, 1 or 2 (Appendix 3) ...See the protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 37 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: E1. Patient with a documented mutation in PDGFRA exon 18 (D842V substitution). E2. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: • Active peptic ulcer disease • Known intraluminal metastatic lesions with risk of bleeding • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: • Malabsorption syndrome • Major resection of the stomach or small bowel E3. Any active/uncontrolled infection, including known infection with HIV, Hepatitis B or Hepatitis C E4. Corrected QT interval (QTc) > 480 msecs using Bazett’s formula E5. History of any one or more of the following cardiovascular conditions within the past 6 months prior to the first dose of study drug: • Cardiac angioplasty or stenting • Myocardial infarction • Unstable angina • Coronary artery bypass graft surgery • Symptomatic peripheral vascular disease • Class III or IV congestive heart failure, as defined by the New York Heart Association(NYHA) classification E6. Poorly controlled arterial hypertension (Systolic blood pressure: 150mmHg / Diastolic blood pressure: 90mmHg). Note: Patients with high blood pressure can be enrolled provided that the hypertension is well controlled at a stable dose of antihypertensive therapy for at least 1 week prior to lenvatinib start). E7. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major). ...See the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the antitumor efficacy of lenvatinib versus placebo in patients with locally advanced or metastatic GIST after failure of imatinib and sunitinib. ;Secondary Objective: Secondary objectives of the blinded part of the study are to determine in both arms: • The Overall Survival (OS) • The Objective Response Rate (ORR)* • The Best Overall Response (BOR)* • The quality of Life (EORTC QLQ-C30) • The tolerance profile In patients from the placebo arm who switched into the active treatment group, the following additional objectives will be studied from lenvatinib initiation: • The Progression-Free Survival (PFS)* • The Objective Response Rate (ORR)* • The Best Overall Response (BOR)* • The quality of Life (EORTC QLQ-C30) • The tolerance profile ;Primary end point(s): The primary endpoint will be the Progression-Free Survival (PFS);Timepoint(s) of evaluation of this end point: PFS Assessed locally by the investigational staff, according to the RECISTv1.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival is defined as the time from the date of randomisation until the date of death due to any cause. Objective Response Rate (ORR) is the proportion of patients with a Complete Response or Partial Response as Best Overall Response. Best Overall Response (BOR) is described as the proportion of patients with a best overall response of Complete Response. The patient’s Quality of Life will be assessed using the EORTC QLQ-C30. The tolerance profile will be described mainly on the frequency of adverse events coded using the common toxicity criteria (NCI-CTC v5.0) grade.;Timepoint(s) of evaluation of this end point: Tumor assessment at a beginning and throughout the study | — |
Countries
France
Contacts
Public ContactJulien
Centre Léon Bérard
Outcome results
None listed