Determination of Intratumoral Concentrations of Kinase Inhibitors in Patients With Advanced Solid Malignancies.

Pilot Study on the Determination of Intratumoral Concentrations of Kinase Inhibitors in Patients With Advanced Solid Malignancies.

The purpose of this study is to determine intratumoral concentration of kinase inhibitors upon 2 weeks of treatment in tumor tissue of patients.

Patients will be cohort-wise treated with clinically available kinase inhibitors for 2 weeks prior to standard palliative treatment. Five patients will be included in each of eight drug cohorts. Biopsies will be performed to determine intratumoral drug concentrations and to compare tissue (phospho)proteomic and kinase activity profiles before and during therapy.

Inclusion Criteria:

• Advanced solid malignancy
• minimum age 18 years
• indication for palliative treatment
• measurable disease with at least one lesion accessable for biopsy

Exclusion Criteria:

• Cardiovascular conditions including congestive heartfailure NYHA class >2
• recent myocardial infarction or uncontrolled coronary artery disease
• cardiac arrhythmias requiring anti-arrhythmic therapy
• uncontrolled hypertension
• uncontrolled infections
• serious non-healing wound, ulcer or bone fracture
• pregnant or breast feeding