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

NCT02071719 | Terminated

• 1 other identifier: 2012/109
• Study Type: observational
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Cell Cancer

Outcome Measures

Primary Outcomes (2)

• Response to treatment

  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

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

Secondary Outcomes (6)

• 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

• 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

• serum proteomic profiles

  Sample collection at inclusion is mandatory (1). Collection after 2-4 weeks of treatment (2) and upon progression (3) are optional

• 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

• 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

Study Arms (5)

Sunitinib

Sorafenib

Everolimus

Pazopanib

Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with renal cell cancer

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• M. Labots: lead

Study Sites (1)

VU Medical Center

Amsterdam, North Holland, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: December 11, 2012
• First Posted: February 26, 2014
• Study Start: April 1, 2012
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: November 20, 2020

Record last verified: 2020-11

Locations

NL (1)