Advanced or metastatic cancer
Conditions
Interventions
Core phase: On day 1 every patient will receive 20 mg LBH589 followed by
5 x 400 mg ketoconazole (day 5 - 9).
Extension phase: 3x weekly (Monday-Wednesday * Friday) 20 mg LBH589
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Histologically proven solid tumor which is advanced or metastatic as documented by CT-scan or MRI * Patients with non-Hodgkin*s lymphoma should have at least one measurable or evaluable lesions (Cheson response criteria for NHL ) * Patient*s disease must have progressed on or following standard therapies. * ECOG performance status of * 2. * Life expectancy of * 12 weeks. * Patients must have the following lab results: - Absolute neutrophil count (ANC) * 1.5 x 10 9/L - Hemoglobin (Hgb) * 9g/dl - Platelets (plt) * 100 x 109/L - AST/SGOT and ALT/SGPT * 2.5 x upper limit of normal (ULN); if known with liver metastases: AST/SGOT and ALT/SGPT * 5.0 x (ULN) - Serum bilirubin * 1.5 x ULN - Calculated creatinine clearance * 50 ml/min - Free T4 within normal limit (WNL) and TSH * ULN - Serum potassium * the lower limit of normal (LLN) - Serum total calcium, magnesium and phosphorus * LLN * Screening ECG with a QTc * 450 msec. * Negative serum or urine pregnancy test 72 hours prior to the administration of the first study treatment. * Baseline LVEF * the lower limit of the institutional normal
Exclusion criteria
Exclusion criteria: * CNS involvement or brain metastases. * Chronic liver toxicity * Impairment of gastrointestinal (GI) function or GI obstruction that may significantly alter the absorption of oral LBH589. * Diarrhea >CTCAE grade 1 * Current chemotherapy, immunotherapy, or radio-therapy or within 4 weeks prior to study entry. * Prior treatment with a HDAC inhibitor including valproic acid within 14 days prior to first dose of LBH589. * Significant cardiac disease, including any one of the following: - Congenital long QT syndrome, history of sustained ventricular tachycardia, history of ventricular fibrillation or torsades de pointes, bradycardia (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary variables that will be evaluated are AUC0-tlast, AUC0-*, and Cmax of LBH589. For the DDI analysis, the combination treatment (Keto + LBH589) will be the test and LBH589 alone will be the reference. | — |
Secondary
| Measure | Time frame |
|---|---|
| The best overall response will be estimated by using the efficacy population and devide this number by the total number of patients with confirmed complete response (CR) or confirmed partial response (PR) divided. Only treatment emergent adverse events (AE) will be summarized. Treatment emergent AEs are defined as those that started on or after the study medication but not after 28 days post the last dose of study medication, or those that started before study medication but worsened. Laboratory data, data from ECGs, vital signs and any other information collected will be listed as appropriate. | — |
Countries
Netherlands
Outcome results
None listed