A Phase I Trial of AVN944, an IMPDH Inhibitor, in Adults With Advanced Stage Solid Tumors

Summary

Background: * AVN944 is an experimental cancer treatment drug, not yet approved by the U.S. Food and Drug Administration. To date, AVN944 as a single drug has been tested in several studies involving humans, including healthy volunteers, patients with leukemia, and patients with advanced pancreatic cancer. * More research is needed to determine the safety and effectiveness of AVN944. Objectives: * To determine the safety of AVN944. * To determine the maximum tolerated dose (the highest dose that does not cause unacceptable side effects) of AVN944. * To see if AVN944 has any effect on patients' tumors. * To learn how the body breaks down AVN944. Eligibility: * Patients 18 years of age and older who have advanced stage solid tumors for which standard therapies do not exist or are no longer effective. Design: * Participants will have a screening visit and five clinic visits during the first treatment cycle. Additional treatment cycles will involve two clinic visits during each 28-day cycle. After participation in the study ends, patients will be asked to return within 28 days after the last dose of study drug for final study procedures. * Evaluations before the treatment period: * Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant. * Questions about medications and side effects. * Blood and urine tests. * Disease evaluation with CT, chest x-ray, and additional laboratory tests depending on the type of cancer. * All patients will have blood samples taken at each visit. * Patients will take specific doses of AVN994 as directed by researchers, and will be asked to keep a diary to record their doses and any side effects. They will be monitored with frequent blood draws at each study visit to provide information on the safety and effectiveness of the drug. * During different cycles, patients will have their disease evaluated by researchers and will be asked if they wish to continue taking AVN994 as part of the study.

Timeline

Start

2009-04

Primary completion

2010-03

Completion

2010-03

Publications

• Background Sintchak MD, Fleming MA, Futer O, Raybuck SA, Chambers SP, Caron PR, Murcko MA, Wilson KP. Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid. Cell. 1996 Jun 14;85(6):921-30. doi: 10.1016/s0092-8674(00)81275-1.
• Background Allison AC, Hovi T, Watts RW, Webster AD. The role of de novo purine synthesis in lymphocyte transformation. Ciba Found Symp. 1977;(48):207-24. doi: 10.1002/9780470720301.ch13.
• Background Jackson RC, Weber G, Morris HP. IMP dehydrogenase, an enzyme linked with proliferation and malignancy. Nature. 1975 Jul 24;256(5515):331-3. doi: 10.1038/256331a0. No abstract available.

Drugs

Indications