Pazopanib and ARQ 197 for Advanced Solid Tumors

Summary

Background: \- Pazopanib is an anticancer drug that blocks the growth of new blood vessels in tumors. It has been approved to treat renal cell cancer and soft tissue sarcomas in patients who have received prior chemotherapy. ARQ 197 (Tivantinib) is an experimental drug that blocks a protein called mesenchymal-epithelial transition factor (c-MET), which cancer cells need to grow. Studies suggest that some drugs that block blood vessel growth can increase the production of c-MET in tumors, which helps cancer cells keep growing. Blocking both blood vessel growth and c-MET with pazopanib and ARQ 197 may help kill cancer cells faster. This study will use these drugs to treat solid tumors that have not responded to earlier treatments. Objectives: \- To test the safety and effectiveness of pazopanib and ARQ 197 for advanced solid tumors. Eligibility: \- Individuals at least 18 years of age who have advanced solid tumors that have not responded to earlier treatments. Design: * Participants will be screened with a physical exam and medical history. They will also have blood and urine tests, and imaging studies. * The study drugs will be given in 4-week cycles of treatment. Participants will take pazopanib once a day and ARQ 197 twice a day by mouth. Some participants will start with pazopanib or ARQ 197 alone for the first week. Then they will take both drugs together for the rest of the study. * Participants will be monitored with frequent blood tests and imaging studies. Optional tumor samples may be collected during different treatment cycles.

Timeline

Start

2012-01-23

Primary completion

2014-09-30

Completion

2016-02-11

Publications

• Background Gerritsen ME, Tomlinson JE, Zlot C, Ziman M, Hwang S. Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells. Br J Pharmacol. 2003 Oct;140(4):595-610. doi: 10.1038/sj.bjp.0705494. Epub 2003 Sep 22.
• Background Xin X, Yang S, Ingle G, Zlot C, Rangell L, Kowalski J, Schwall R, Ferrara N, Gerritsen ME. Hepatocyte growth factor enhances vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Am J Pathol. 2001 Mar;158(3):1111-20. doi: 10.1016/S0002-9440(10)64058-8.
• Background Van Belle E, Witzenbichler B, Chen D, Silver M, Chang L, Schwall R, Isner JM. Potentiated angiogenic effect of scatter factor/hepatocyte growth factor via induction of vascular endothelial growth factor: the case for paracrine amplification of angiogenesis. Circulation. 1998 Feb 3;97(4):381-90. doi: 10.1161/01.cir.97.4.381.

Drugs

Indications