A Randomized Phase II Non-Comparative Study of SB-715992 Given Weekly or Every Three Weeks in Advanced or Metastatic Colorectal Cancer
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.
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
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
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response (CR or PR) as determined by the RECIST criteria
Up to 5 years
Beckman Research Institute
United States: Food and Drug Administration
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