Advanced Solid Tumors, Cancer
Conditions
Brief summary
The purpose of this study is to determine intratumoral concentration of kinase inhibitors upon 2 weeks of treatment in tumor tissue of patients.
Detailed description
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.
Interventions
DRUGSunitinib
50 mg once daily, oral use, 14 days
DRUGSorafenib
400 mg, twice daily, oral use, 14 days
DRUGErlotinib
150 mg once daily, oral use, 14 days
DRUGEverolimus
10 mg once daily, oral use, 14 days
DRUGLapatinib
1250 mg once daily, oral use, 14 days
DRUGDasatinib
100 mg once daily, oral use, 14 days
DRUGPazopanib
800 mg once daily, oral use, 14 days
DRUGVemurafenib
960 mg twice daily, oral use, 15-21 days
PROCEDUREtumor biopsy
PROCEDUREskin biopsy (optional)
Sponsors
Amsterdam UMC, location VUmc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| concentrations of intratumoral kinase inhibitors upon 2 weeks of treatment | 2 weeks |
Secondary
| Measure | Time frame |
|---|---|
| kinase inhibitor concentrations in plasma, serum and PBMC's upon 2 weeks of treatment | 2 weeks |
| intra-dermal kinase inhibitor concentrations upon 2 weeks of treatment | 2 weeks |
| To determine per patient whether 2 weeks of treatment with kinase inhibitors induces significant change of phosphoproteomic profiles in tumor tissue | 2 weeks |
| To determine per patient whether 2 weeks of treatment with kinase inhibitors induces significant change of kinase activity in tumor tissue | 2 weeks |
Countries
Netherlands
Outcome results
None listed