Clinical trial NCT02071719: Prediction of Response to Kinase Inhibitors Based on Protein Phosphorylation Profiles in Tumor Tissue From Advanced Renal Cell Cancer Patients
Official title: Prediction of Response to Kinase Inhibitors Based on Protein Phosphorylation Profiles in Tumor Tissue From Advanced Renal Cell Cancer Patients
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Renal Cell Cancer
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2014-02-26
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with renal cell cancer

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Response to treatment
timeFrame: Follow up once every 4 months until disease progression or death of the patient
measure: Progression Free Survival
timeFrame: once every 4 months until disease progression or death of the patient
Secondary outcomes:
measure: PamChip kinase activity profiling and PFS
timeFrame: Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
measure: genome-wide mutational profiles by Massively Parallel Sequencing (MPS)
timeFrame: Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
measure: serum proteomic profiles
timeFrame: Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
measure: the value of the frequency and phenotype of immunoregulatory cells in blood and tumor tissue
timeFrame: Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
measure: genetic polymorphisms and pharmacokinetic parameters
timeFrame: Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
measure: tumor exosomes from urine and serum
timeFrame: Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU Medical Center
state: Noord Holland
Study officials:
References: