A Phase 1-2, Multicenter, Open-Label Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 Given in Combination With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer
Apoptotic induction in cancer cells is a sought after therapeutic goal. Most successful
anticancer agents activate apoptosis pathways in the cancers they treat. Apoptotic pathways
in cells appear to converge on a single family of enzymes, the caspases, which are proteases
that dismantle the cell in an orderly, non-inflammatory fashion, resulting in cell death.
The X-linked Inhibitor of Apoptosis (XIAP) is the only known cellular inhibitor of caspases,
its over expression thereby blocking the principal means of apoptosis. A wide range of
evidence indicates that cellular overexpression of members of the IAP family is a
fundamental means by which many cancer cells evade death, even in the presence of strong
extrinsic (death receptor-mediated) and intrinsic (mitochondria-mediated) apoptotic cues.
The inhibition of cellular XIAP activity, specifically in cancer cells under stress and
primed for apoptosis by chemotherapeutic agents, is viewed as a powerful means of tipping
the balance towards cell death. In particular, XIAP down regulation has been shown to
enhance taxane cytotoxicity preclinically. AEG35156 is a second generation antisense which
targets XIAP mRNA to lower XIAP levels and the apoptotic threshold of cancer cells,
enhancing their sensitivity to intrinsic death and chemotherapy. AEG35156 may thus enhance
the anticancer activity of carboplatin and paclitaxel in patients with advanced non small
cell lung cancer
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the recommended dose of AEG35156 when used in combination with carboplatin and paclitaxel and if the dose can enhance the response rate of carboplatin and paclitaxel in patients with advanced non small cell lung cancer.
2 years
No
Robert M Jotte, MD
Principal Investigator
Rocky Mountain Cancer Centers
United States: Food and Drug Administration
AEG35156-203
NCT00558922
September 2007
October 2009
Name | Location |
---|---|
Virginia Oncology Associates | Newport News, Virginia 23606 |
Rocky Mountain Cancer Center | Denver, Colorado 80218 |
Cancer Centers of the Carolinas | Greenville, South Carolina 29605 |
Central indiana Cancer Center | Indianapolis, Indiana 46227 |
Dayton Oncology & Hematology, P.A. | Kettering, Ohio 45409 |
Northwest Cancer Specialists, P. C. | Vancouver, Washington 98684 |