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Prediction of response to kinase inhibitors based on protein phosphorylation profiles in tumor tissue from advanced renal cell cancer patients.


- candidate number13799
- NTR NumberNTR3710
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR14-nov-2012
- Secondary IDs2012/109 METC VUmc
- Public TitlePrediction of response to kinase inhibitors based on protein phosphorylation profiles in tumor tissue from advanced renal cell cancer patients.
- Scientific TitlePrediction of response to kinase inhibitors based on protein phosphorylation profiles in tumor tissue from advanced renal cell cancer patients.
- ACRONYMPhosphoproteomics for prediction of response to treatment in kidney cancer
- hypothesisThe 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 targeterd 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 phosphoprotemics may be a potential clinical diagnostic tool to predict for tumor response to targeted therapy. This approach is expected to increase efficacy, reduce costs an d prevent toxicities from (ineffective) targeted agents.
- Healt Condition(s) or Problem(s) studiedRenal cell cancer, Kinase inhibitors, Phosphoproteomics
- Inclusion criteria1. Patients with advanced (unresectable and/or metastatic) renal cell cancer;
2. Patients who will start treatment with sunitinib, pazopanib, sorafenib, axitinib or everolimus;
3. At least one tumor lesion should be accessible for biopsy. bone metastases are excluded as possible biopsy site;
4. Age >- 18 years;
5. 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);
6. WHO performance status 0 - 2;
7. Able to provide written informed consent.
- Exclusion criteria1. Clinical findings associated with an unacceptably high tumor biopsy risk, according to the judgement of the investigator;
2. Radiotherapy on target lesions during study or within 4 weeks of the start of study drug;
3. Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.
- mec approval receivedyes
- multicenter trialyes
- randomisedyes
- masking/blindingNone
- controlNot applicable
- groupParallel
- TypeSingle arm
- Studytypeobservational
- planned startdate 2-nov-2012
- planned closingdate1-apr-2014
- Target number of participants225
- InterventionsIn this study, a fresh tumor biopsy from a metastasis or a primary tumor will be taken. In all subjects subsequent standard treatment will be initiated according to current clinical guidelines. In addition to this biopsy, collection of urine and blood is performed upon inclusion and the same procedure is optional on 2 other time points during treatment.
- Primary outcomeThe phosphoproteomics profile of the tumor biopsy before treatment will be determined and correlated with radiological response and progression-free survival.
- Secondary outcome1. The relationship between the PamChip kinase activity profile for the initiation of therapy and progression-free survival;
2. The relationship between the genetic mutation profile of the primary tumor based on MPS and progression-free survival;
3. The relationship between the serum peptide profile before and during treatment and progression-free survival;
4. The relationship between the number and type of immune regulatory cells in blood and tissue and progression-free survival;
5. The relationship between genetic polymorphisms and pharmacokinetic parameters and progression-free survival;
6. The relationship between protein profile tumorexosomen from urine and serum and progression-free survival.
- TimepointsA feasability analysis will be performed when 20 patients are included.
- Trial web siteN/A
- statusopen: patient inclusion
- CONTACT FOR PUBLIC QUERIESProf. dr. H.M.W. Verheul
- CONTACT for SCIENTIFIC QUERIESProf. dr. H.M.W. Verheul
- Sponsor/Initiator VU University Medical Center
- Funding
(Source(s) of Monetary or Material Support)
VitrOmics Health Services BV (VHS)
- PublicationsN/A
- Brief summaryThe 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.
- Main changes (audit trail)
- RECORD14-nov-2012 - 1-dec-2012


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