SB-715992 in Treating Patients With Advanced or Metastatic Colorectal Cancer

PRIMARY OBJECTIVES: I. To determine the objective response rate in patients with advanced or metastatic colorectal cancer treated with SB-715992 once a week for 3 weeks, every 28 days and SB-715992 once every 21 days. SECONDARY OBJECTIVES: I. To determine the time to tumor progression, progression free and overall survival of patients and toxicity in patients with advanced or metastatic colorectal cancer treated with SB-715992 once a week for 3 weeks, every 28 days and SB-715992 once every 21 days. II. To characterize the population pharmacokinetic (PK) parameters of SB-715992 including an assessment of significant covariates on SB-715992 PK and an assessment of the potential relationships between the pharmacokinetics of SB-715992 and relevant safety and efficacy endpoints. IV. To examine cytoskeletal morphology changes in response to SB-715992 in peripheral blood mononuclear cells and tumors by fluorescent immunohistochemistry. V. To evaluate mRNA expression of betaΙΙΙ-tubulin and KSP in archival tumor tissue. VI. To determine the frequency of genomic polymorphisms in genes targeted by SB-715992 (measured in peripheral blood mononuclear cells) and to assess whether germline polymorphisms (DNA) of genes targeted by SB-715992 (KSP inhibitor) are associated with toxicity and clinical outcome in patients with colorectal cancer. Further, whether genes involved with the metabolism (CYP3A4) and resistance (MDR1) affect the outcome in these patients. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive SB-715992 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.