A Pilot Study of EZN-2968, an Antisense Oligonucleotide Inhibitor of HIF-1alpha, in Adults With Advanced Solid Tumors With Liver Metastases

Summary

Background: \- A protein called HIF is believed to be involved both in forming cancers and helping them to grow after they are formed. EZN-2968 is a new type of cancer drug that goes into the cancer cell and switches off the production of the HIF protein. Researchers are interested in testing EZN-2968 in people who have liver cancer because studies have shown that this drug travels to the liver and stays there when the drug is given through a vein. Objectives: \- To determine the safety and effectiveness of EZN-2968 on liver cancer. Eligibility: \- Individuals 18 years of age and older who have been diagnosed with liver cancer that has not responded to standard treatments. Design: * Participants will have an initial screening visit with a physical examination, blood and urine tests, and imaging studies to assess tumor size. Tumor biopsies may also be taken for research purposes. * Participants will have an undefined number of 6-week treatment cycles of EZN-2968, given once a week for 3 weeks followed by 3 weeks without the drug. * During each cycle, participants will have additional blood tests and imaging scans to assess tumor response to treatment. * Cycles of treatment with EZN-2968 may continue until the treatment is not effective, illness requires participants to stop taking the study drug, or the participant chooses to withdraw from the study.

Timeline

Start

2010-04-29

Primary completion

—

Completion

2013-09-24

Publications

• Background Wenger RH, Rolfs A, Marti HH, Guenet JL, Gassmann M. Nucleotide sequence, chromosomal assignment and mRNA expression of mouse hypoxia-inducible factor-1 alpha. Biochem Biophys Res Commun. 1996 Jun 5;223(1):54-9. doi: 10.1006/bbrc.1996.0845.
• Background Semenza GL. HIF-1 and mechanisms of hypoxia sensing. Curr Opin Cell Biol. 2001 Apr;13(2):167-71. doi: 10.1016/s0955-0674(00)00194-0.
• Background Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003 Oct;3(10):721-32. doi: 10.1038/nrc1187.

Drugs

Indications