copanlisib (bay80-6946) drug-drug interaction and cardiovascular safety study in advanced solid tumor and non-hodgkin's lymphoma patients

Conditions: Medical Oncology

Summary: to evaluate the effect of itraconazole or rifampin on the absorption, distribution, metabolism and elimination of copanlisib (bay80-6946). to evaluate the effect of copanlisib on qt/qtc intervals and left ventricular ejection fraction as parameters of cardiovascular safety.


Eligibility criteria:
inclusion criteria: * male or female patients ≥ 18 years of age with histological or cytological confirmed advanced solid tumors or non-hodgkin's lymphoma that have progressed on, or failed to respond to, therapies known to provide clinical benefit may be enrolled after signing informed consent. * normal left ventricular ejection fraction; adequate liver, renal and bone-marrow functions as assessed by laboratory values. * adequate performance status and life expectancy of at least 3 months. exclusion criteria: * solid-tumor patients with central nervous system (cns) metastases if treatment completed \< 3 months before enrollment or lesions unstable or progressing on mri scans performed within 1 month of enrollment or unstable symptoms of the cns metastases. * evidence of ventricular dysfunction such as congestive heart failure (chf) or a history of chf greater than nyha class ii * active coronary artery disease or myocardial infarction within the 6 months before study entry; any new-onset angina within the 3 months before study entry or unstable angina; cardiac arrhythmia requiring anti-arrhythmic therapy. * prior diagnosis of type 1 or 2 diabetes mellitus, hyperglycemia (defined as fasting blood or plasma glucose above 125 mg/dl under 2 separate days, corresponding to 6.94 mmol/l) or hba1c ≥ 7%. * use of systemic including inhaled corticosteroids within the 2 days before the start of study treatment (however, topical steroids are permitted). * known presence of human immunodeficiency virus (hiv) infection or active hepatitis (b or c). * uncontrolled hypertension (systolic blood pressure \[bp\] \>150 mmhg or diastolic blood pressure \> 90 mmhg despite optimal medical management). * anticancer chemotherapy, hormone therapy or immunotherapy within the 4 weeks before the first study treatment or scheduled for administration (of the above) during the study * history of, or concurrent, interstitial lung disease (ild) or severely impaired pulmonary function. * medications with drug-drug interaction potential for itraconazole which is to be excluded before the study and during cycle 1 such as cyp3a4 substrates with a narrow therapeutic window or which have the potential to prolong qtc * concomitant medication contraindicated for use with rifampin (including, but not limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide, triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme a (hmg-coa)-reductase inhibitors metabolised by cyp3a4, such as lovastatin and simvastatin, ergot alkaloids metabolised by cyp3a4, such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine), atazanavir, darunavir, fosamprenavir, ritonavir-boosted saquinavir, saquinavir, or tipranavir

Keywords: phase 1 advanced solid tumor non-hodgkin's lymphoma pi3 kinase inhibitor drug-drug interaction