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

• Register: German Clinical Trials Register
• Last refreshed on: 8 April 2024
• Main ID: DRKS00000657
• Date of registration: 23/12/2010
• Prospective Registration: No
• Primary sponsor: Universitätsklinikum Essen
• Public title: Phase I study of imatinib and LBH589 in imatinib- and sunitinib-refractory gastrointestinal stromal tumors
• Scientific title: Phase I study of imatinib and LBH589 in imatinib- and sunitinib-refractory gastrointestinal stromal tumors - WTZ-GIST-09-01
• Date of first enrolment: 12/07/2010
• Target sample size: 21
• Recruitment status: Complete
• URL: http://drks.de/search/en/trial/DRKS00000657
• Study type: interventional
• Study design: Allocation: Non-randomized controlled study; Masking: Open (masking not used); Control: Other; Assignment: other; Study design purpose: treatment
• Phase: 1

Countries of recruitment

Germany

Contacts

• Name: Sebastian Bauer
• Affiliation: Sarkomzentrum Innere Klinik (Tumorforschung) Universitätsklinikum Essen

• Name: Sebastian Bauer
• Affiliation: Sarkomzentrum Innere Klinik (Tumorforschung) Universitätsklinikum Essen

Key inclusion & exclusion 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: • 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


Age minimum: 18 Years
Age maximum: None
Gender: All

Health Condition(s) or Problem(s) studied

MedDRA - 10051066 Gastrointestinal stromal tumor

Intervention(s)

Group 1: Imatinib 400mg qd d1-28

LBH589 20/30/40mg d8-28 (amount of LBH589 in dependance of studycohort)

Primary Outcome(s)

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 Outcome(s)

• 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)

Secondary ID(s)

2009-011417-24

4035954

Source(s) of Monetary Support

Novartis

Ethics review

Status: Approved
Approval date: 17/06/2010
Contact:

[e-mail]

Ethik-Kommission der Medizinischen Fakultät der Universität Duisburg-Essen

[phone]

[e-mail]

Results

• Results available: Yes
• Date Posted: 26/01/2023
• Date Completed: 30/11/2012
• URL: http://drks.de/search/en/trial/DRKS00000657#studyResults