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Phase II Trial of Intravenous CI-1042 in Patients With Metastatic Colorectal Cancer

Oday Hamid, Mary L. Varterasian, Scott Wadler, J. Randolph Hecht, Al Benson, III, Evanthia Galanis, Margaret Uprichard, Charles Omer, Paul Bycott, Robert C. Hackman, Anthony F. Shields

From the Karmanos Cancer Institute, Wayne State University, Detroit, MI; Montefiore Medical Center, Bronx, NY; University of California at Los Angeles Medical Center, Los Angeles, CA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; The Mayo Clinic, Rochester, MN; and Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA.

Address reprint requests to Oday Hamid, PharmD, Pfizer Global Research and Development, 2800 Plymouth Rd, Ann Arbor, MI 48105; email: oday.hamid{at}pfizer.com.

Purpose: To evaluate the antitumor activity, safety, immune response, and replication of CI-1042 (ONYX-015), an E1B 55-kd gene-deleted replication-selective adenovirus, administered intravenously to patients with metastatic colorectal cancer

Patients and Methods: Eighteen patients with metastatic colorectal cancer for whom prior chemotherapy failed were enrolled onto an open-label, multicenter, phase II study. CI-1042 was administered intravenously at a dose of 2 x 10¹² viral particles every 2 weeks. Patients were evaluated for tumor response and toxicity; in addition, blood samples were taken for adenovirus DNA and neutralizing antibody analysis.

Results: Common toxicities included flu-like symptoms, nausea, and emesis. All 18 patients eventually were removed from study because of progressive disease. Seven patients were assessed as having stable disease after 2 months of treatment, whereas two patients were considered to have stable disease after 4 months. Detectable circulating CI-1042 DNA was identified in 36% of patients 72 hours after last infusion, which is suggestive of ongoing viral replication.

Conclusion: In this phase II study, intravenous CI-1042 was administered safely to patients with advanced colorectal cancer. Toxicity was manageable, consisting primarily of flu-like symptoms. Stable disease was experienced by seven patients for 11 to 18 weeks.

Sponsored by Pfizer Global Research and Development, Department of Clinical Oncology, Ann Arbor, MI.

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