Doxorubicin Pharmacokinetics--Alone &In Comb w/ VX-710

Georgetown University, Washington DC

Investigators

Linked publications & trials

Abstract

Summary: Chemotherapy is one of the main therapeutic interventions in the treatment of cancer. One common form of resistance to chemotherapy has been shown to be due to overexpression of the mdr 1 gene by tumor cells. This gene encodes a protein known as P-glycoprotein (P-gp). P-gp is an integral membrane protein that is capable of transporting diverse substrates out of the cell via energy dependent process. Inhibition of p-gp mediated transport of oncolytic agents has obvious therapeutic advantage, and various types of inhibitory agents have been investigated. VX-710 parenteral solution, an inhibitor of MDR-1 gene product, P-glycoprotein (P-gp), is proposed for the treatment of patients with cancers characterized by resistance to chemotherapeutic agents based upon this mechanism. The objectives of this study are: 1. To determine the pharmacokinetic profile of doxorubicin when given alone and in combination with VX-710. 2. To obtain pharmacokinetic information for VX-710 at the dose of 120 mg/m2/hour administered as a 96 hour infusion in combination with 60 mg/m2 of doxorubicin. 3. To assess the safety and tolerability of 96 hour infusion of VX-710 given in combination with doxorubicin. 4. To document antitumor effect of VX-710 in combination with doxorubicin. Results-To-Date: This study is still recruiting patients and no results are available.