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

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed advanced/metastatic colorectal cancer
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan
* Patients must have received prior therapy (in any setting) with 5-FU, CPT-11, and oxaliplatin; patients may have received prior erbitux and bevacizumab, but it is not required
* Patients must have received at least one prior chemotherapy regimen for advanced disease
* Tumor must be accessible for biopsy or paraffin embedded tissue must be available for review of their biopsy specimen
* Life expectancy of \> 12 weeks
* ECOG performance status 0-2 (Karnofsky \>= 50%)
* Leukocytes \>= 3,000/μL
* Absolute neutrophil count \>= 1,500/μL
* Platelets \>= 100,000/μL
* Hemoglobin \>= 9 mg/dL
* Total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal
* Creatinine =\< 1.5 X institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from AEs due to agents administered more than 4 weeks earlier
* Patients may not have received any other investigational agents within 28 days of study entry
* Patients may not receive other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study
* Prohibited medications; SB-715992 is a moderate to significant in vitro inhibitor of CYP3A4; the following lists of medications/substances are moderate to significant inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may alter study drug exposure; the use of these medications/substances within 14 days (\> 6 months for amiodarone) prior to the administration of the first dose of SB-715992 through discontinuation from the study is prohibited

  * Inhibitors of CYP3A4:

    * Antibiotics: clarithromycin, erythromycin, troleandomycin
    * Antifungals: itraconazole, ketoconazole, fluconazole (doses \> 200 mg/day), voriconazole
    * Antidepressants: nefazodone, fluovoxamine
    * Calcium channel blockers: verapamil, diltiazem
    * Miscellaneous: amiodarone\*, grapefruit juice, bitter orange

      * Use of amiodarone within 6 months prior to the administration of the first dose of SB-715992 is prohibited
  * Inducers of CYP3A4:

    * Anticonvulsants: phenytoin, carbamazepine, Phenobarbital, oxcarbazepine
    * Antibiotics: rifampin, rifabutin, rifapentine
    * Miscellaneous: St. John's wort, modafinil
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to SB-715992
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with SB-715992
* HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study