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

Study Overview
=================
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.

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

Conditions
-----------------
Cancer, Advanced Solid Tumors

Intervention / Treatment
-----------------
* Drug: Sunitinib
* Drug: Sorafenib
* Drug: Erlotinib
* Drug: Everolimus
* Drug: Lapatinib
* Drug: Dasatinib
* Drug: Pazopanib
* Drug: Vemurafenib
* Procedure: tumor biopsy
* Procedure: skin biopsy (optional)


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kinase inhibitor<br>Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor | Drug: Sunitinib<br>* 50 mg once daily, oral use, 14 days<br>Drug: Sorafenib<br>* 400 mg, twice daily, oral use, 14 days<br>Drug: Erlotinib<br>* 150 mg once daily, oral use, 14 days<br>Drug: Everolimus<br>* 10 mg once daily, oral use, 14 days<br>Drug: Lapatinib<br>* 1250 mg once daily, oral use, 14 days<br>Drug: Dasatinib<br>* 100 mg once daily, oral use, 14 days<br>Drug: Pazopanib<br>* 800 mg once daily, oral use, 14 days<br>Drug: Vemurafenib<br>* 960 mg twice daily, oral use, 15-21 days<br>Procedure: tumor biopsy<br> <br> Procedure: skin biopsy (optional)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| concentrations of intratumoral kinase inhibitors upon 2 weeks of treatment |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |