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

Not Applicable

Completed

• Conditions: Advanced Solid Tumors; Cancer
• Interventions: Drug: Sunitinib; Drug: Sorafenib; Drug: Erlotinib; Drug: Everolimus; Drug: Lapatinib; Drug: Dasatinib; Drug: Pazopanib; Drug: Vemurafenib; Procedure: tumor biopsy; Procedure: skin biopsy (optional)

• Registration Number: NCT01636908
• Lead Sponsor: Amsterdam UMC, location VUmc

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.

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2012-07-05
• Study First Submitted QC: 2012-07-09
• Study First Posted: 2012-07-10
• Primary Completion: 2018-01-01
• Study Completion: 2019-12-01
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-14
• Last Update Posted: 2021-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Kinase inhibitor	Vemurafenib	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	tumor biopsy	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	skin biopsy (optional)	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	Sunitinib	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	Pazopanib	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	Everolimus	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	Erlotinib	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	Sorafenib	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	Lapatinib	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor
Kinase inhibitor	Dasatinib	Patients are cohort-wise treated with a registered (tyrosine) kinase inhibitor

Primary Outcome Measures

Name	Time	Method
concentrations of intratumoral kinase inhibitors upon 2 weeks of treatment	2 weeks

Secondary Outcome Measures

Name	Time	Method
To determine per patient whether 2 weeks of treatment with kinase inhibitors induces significant change of kinase activity in tumor tissue	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
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

Trial Locations

Locations (1)

VUMedical Center; 🇳🇱 Amsterdam, Netherlands