Prediction of Response to Kinase Inhibitors Based on Protein Phosphorylation Profiles in Tumor Tissue From Advanced Renal Cell Cancer Patients

N/ATerminatedNCT02071719

M. Labots6 enrolled

Overview

The rapid development of agents blocking kinases has established the use of molecularly targeted therapy as the preferred treatment approach for patients with metastatic renal cell cancer (RCC). Five kinase inhibitors (sunitinib, everolimus, temsirolimus, sorafenib and pazopanib) are now approved for clinical use. Response rates differ among these agents, importantly depending on line of treatment. In first-line treatment sunitinib results in 47% objective response rates, where in second-line after cytokines 34% responds. Thus far, it is unclear which patient with advanced renal cell cancer will respond to targeted therapy. In order to select patients for targeted therapies, several profiling approaches have been explored but to date no adequate and reliable test is available. It is assumed that responses to targeted agents depend on specific receptor and protein signalling activities in tumor tissues. Therefore, we propose that protein phosphorylation profiling with phosphoproteomics may be a potential clinical diagnostic tool to predict for tumor response to targeted therapy.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Renal Cell Cancer

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with advanced (unresectable and/or metastatic) renal cell cancer. * Patients who will start treatment with sunitinib, pazopanib, sorafenib, axitinib or everolimus. * At least one tumor lesion should be accessible for biopsy. Bone metastases are excluded as possible biopsy site. * Age \>- 18 years. * Patients must have at least one measurable lesion. Lesions must be evaluated by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST). * WHO performance status 0 - 2 * Able to provide written informed consent Exclusion Criteria: * Clinical findings associated with an unacceptably high tumor biopsy risk, according to the judgement of the investigator. * Radiotherapy on target lesions during study or within 4 weeks of the start of drug. * Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.

Outcomes

Primary Outcomes

Response to treatment

Time frame: Follow up once every 4 months until disease progression or death of the patient

Progression Free Survival

To determine the relation between tumor tissue phosphoproteomic profiles and progression-free survival (PFS) in patients with advanced RCC

Time frame: once every 4 months until disease progression or death of the patient