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Proposal 654

Title of the Proposed Research

Development of Population Pharmacokinetic/Pharmacodynamic Models for Pazopanib within the EuroTARGET project (Workpackage 7)

Lead Researcher

Ulrich Jaehde, PhD

Affiliation

University of Bonn
Germany

Funding Source

This project receives funding from the European Union’s Seventh Framework Program (FP7/2007-2013) under grant agreement no 259939.

Potential Conflicts of Interest

None

Data Sharing Agreement Date

15 Jan 2015

Lay Summary

EuroTARGET is a European collaborative project on "Targeted therapy in Renal cell cancer: Genetic and Tumour related biomarkers for response and toxicity". It is funded by the European Commission under the Seventh Framework Programme (FP7). The project brings together 14 partner organisations (12 research institutes and 2 companies) from 8 European countries (www.eurotargetproject.eu).

Since a few years, specific drugs are available for patients with metastasized renal cell cancers that can suppress the development of new blood vessels in the tumor. However, not all patients show clinical benefit from therapy. In addition to this, toxicity is experienced by a substantial number of patients. And such toxicity frequently necessitates a reduction of the dose or even cessation of therapy. In individual patients, it is impossible to accurately predict response and toxicity. That means that many patients will be treated with the drugs while they will experience only side effects without any benefits. On the other hand, other patients may be treated with a suboptimal type of drug or dose.

The EuroTARGET project aims to collect specific information that will help to quickly predict the outcome of an individual’s treatment. This will allow physicians to effectively optimize a treatment regimen to target a patient’s individual condition. The specific information the EuroTARGET researchers are looking for are so-called biomarkers. A biomarker is a term often used to refer to a protein measured in blood whose concentration reflects the presence or severity of a disease.

In order to take inter-individual variability of drug and biomarker concentrations into account, a phase IV pharmacokinetic/pharmacodynamic (PK/PD) sub-study (EuT-PK/PD, Workpackage 7) focussing on sunitinib is being conducted in 10 German centers. Recently, this study was extended to pazopanib. Overall 1100 patients will be recruited in Europe, 100 will additionally participate in the PK/PD sub-study. The final goal of this work is to develop predictive PK/PD models for sunitinib and pazopanib which may assist the treating physician to individualize drug therapy.

In the proposed research, pharmacokinetic data from previous clinical trials will be used as a basis for the development of predictive PK/PD models for pazopanib.

Study Data Provided

Study MD1113555: A two-part study to evaluate the safety, tolerability and pharmacokinetics of single and repeat oral doses of pazopanib in healthy adult subjects
Study VEG10004: An Open-Label, Two-Part Study to Characterize the Pharmacokinetics of a Single Intravenous Dose of Pazopanib (GW786034) and the Absorption, Distribution, Metabolism and Elimination of a Single Oral [14C] Labeled Dose of Pazopanib in Subjects with Solid Tumor Malignancies
Study VEG111485: A Phase I, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Effect of Repeat Oral Doses of Pazopanib (GW786034) on Cardiac Conduction in Subjects with Solid Tumors

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation