Phase I study of imatinib and LBH589 in imatinib- and sunitinib-refractory gastrointestinal stromal tumors

Phase 1

• Conditions: MedDRA - 10051066 Gastrointestinal stromal tumor

• Registration Number: DRKS00000657
• Lead Sponsor: niversitätsklinikum Essen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-23
• Results First Posted: 2012-06-04
• Study Completion: 2012-11-30
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 12

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

•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

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.<br>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) <br>

Secondary Outcome Measures

Name	Time	Method
• Safety and tolerability of panobinostat (LBH589) in combination with imatinib including acute and chronic toxicities, in these patients.<br>• Single-dose and repeated-dose pharmacokinetic assessments of panobinostat (LBH589) in combination with imatinib therapy in these patients.<br>• 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<br>• Relationship between clinical outcome, primary and secondary mutations of c-KIT or c-PDGFRA (optional) <br>• Time to response (SD, PR or CR), time to progression and response duration based on RECIST criteria (follow-up part of the trial)<br>• PFS at month 12 for patients with data available from follow up observation (follow-up part of the trial) <br>