MedDRA - 10051066 Gastrointestinal stromal tumor
Conditions
Interventions
Group 1: Imatinib 400mg qd d1-28
LBH589 20/30/40mg d8-28 (amount of LBH589 in dependance of studycohort)
Sponsors
Universitätsklinikum Essen
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: • Histologically proven diagnosis of GIST • Objectively documented evidence of progressive disease according to modified RECIST criteria despite at least 2 months' continuous treatment with Imatinib at a dosage of 800 mg/day and progressive disease despite at least 3 months continous treatment with Sunitinib at 50mg/day (4 weeks on 2weeks off or 37.5mg continous dosing) or intolerance to each of the drugs at the above described dosing schedules. Patients with intolerance to imatinib at a dose of 800mg must have tolerated imatinib at the 400mg dose-level • Adequate bone marrow, liver and renal function on imatinib treatment, as shown by: WBC = 3 x 109/L, Absolute neutrophil count (ANC) = 1.5 x 109/L, Hemoglobin = 9 g/dL, Platelet count = 100 x 109/L, Serum transaminase activity (AST/SGOT & ALT/SGPT) < 2.5 X ULN, Serum total bilirubin < 1.5 x ULN, Serum creatinine < 1.5 x ULN, or a creatinine clearance of = 60 mL/min.
Exclusion criteria
Exclusion criteria: • Patients presenting with known or symptomatic CNS metastases or leptomeningeal involvement • History of cardiac disease: congestive heart failure (> New York Heart Association class 2), active coronary artery disease, cardiac arrhythmias requiring anti- arrhythmic therapy other than beta blockers or digoxin, uncontrolled hypertension; myocardial infarction more than 6 month prior to study entry is permitted. Patients that have received other HDAC-inhibitors alone or in combination with imatinib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| After the first cycle: Determination of maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of escalating doses of LBH589 (panobinostat) in combination with imatinib in patients with GIST who have failed or are intolerable to imatinib and sunitinib treatment. Determination of maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) by description of adverse events according to CTC AE criteria (physical examination, laboratory parameters, electrocardiogram, echocardiography and patient questionaire) | — |
Secondary
| Measure | Time frame |
|---|---|
| • Safety and tolerability of panobinostat (LBH589) in combination with imatinib including acute and chronic toxicities, in these patients. • Single-dose and repeated-dose pharmacokinetic assessments of panobinostat (LBH589) in combination with imatinib therapy in these patients. • Preliminary efficacy of panobinostat (LBH589) plus imatinib in patients with gastrointestinal stromal tumor (GIST). Efficacy is defined as the metabolic response as defined by the EORTC-PET Study Group Criteria • Relationship between clinical outcome, primary and secondary mutations of c-KIT or c-PDGFRA (optional) • Time to response (SD, PR or CR), time to progression and response duration based on RECIST criteria (follow-up part of the trial) • PFS at month 12 for patients with data available from follow up observation (follow-up part of the trial) | — |
Countries
Germany
Contacts
Public ContactSebastian Bauer
Sarkomzentrum Innere Klinik (Tumorforschung) Universitätsklinikum Essen
Outcome results
None listed