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

Renal Cell Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02071719
• Other study ID #: 2012/109
• Status: Terminated
• Start date: April 2012
• Est. completion date: October 2017

Study information

• Verified date: November 2020
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Renal Cell Cancer

Locations

Country	Name	City	State
Netherlands	VU Medical Center	Amsterdam	Noord Holland

Sponsors (1)

Lead Sponsor	Collaborator
M. Labots

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response to treatment		Follow up once every 4 months until disease progression or death of the patient
Primary	Progression Free Survival	To determine the relation between tumor tissue phosphoproteomic profiles and progression-free survival (PFS) in patients with advanced RCC	once every 4 months until disease progression or death of the patient
Secondary	PamChip kinase activity profiling and PFS		Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
Secondary	genome-wide mutational profiles by Massively Parallel Sequencing (MPS)		Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
Secondary	serum proteomic profiles		Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
Secondary	the value of the frequency and phenotype of immunoregulatory cells in blood and tumor tissue		Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
Secondary	genetic polymorphisms and pharmacokinetic parameters		Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional
Secondary	tumor exosomes from urine and serum		Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional