Phase I Trial of huA33 Plus Chemotherapy in Patients With Metastatic Colorectal Cancer

Summary

Although treatment for metastatic colorectal cancer has improved significantly over the recent years, it still remains a significant health problem representing the leading cancer by incidence in the United States of America. In the search for new therapies, monoclonal antibodies have been developed to specifically target human colon cancer cells. huA33 is an antibody that reacts with the A33 antigen which is produced by colorectal cancers. Prior studies have shown that administration of the huA33 antibody may delay the growth of tumor cells producing the specific antigen. Oxaliplatin and 5-fluorouracil (5-FU) are cytotoxic agents which are considered as standard treatment in metastatic colorectal cancer. Leucovorin (folinic acid) is a vitamin which enhances the effect of 5-FU. Eligible patients with advanced colorectal cancer will receive huA33 10 mg/m2 by intravenous (IV) infusion weekly for twelve weeks. Starting on Study Day 15 (week 3), 5-FU, leucovorin, and oxaliplatin will be administered every 2 weeks for 10 weeks. Patients will be evaluated weekly for toxicity. Blood samples will be obtained every week for hematology and serum biochemistry analysis and for determination of human anti-human antibodies (HAHA). In patients with measurable disease, tumors will be assessed by the appropriate scan at baseline and at the end of the thirteen week cycle. The primary objective of this study is to assess the safety of huA33 + 5-FU + leucovorin + oxaliplatin. The secondary objective is to measure the immunogenicity of huA33 when given in combination with 5-FU plus leucovorin and oxaliplatin and to document tumor responses.

Timeline

Start

2005-04-18

Primary completion

2006-11-08

Completion

2016-04-01

Publications

• Background Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

Drugs

Indications