Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer

Inclusion Criteria:

* Histologically or cytologically confirmed colorectal cancer

  * Metastatic disease
  * Not curable by surgical resection
  * Archival tumor tissue available
* Measurable disease, defined as at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

  * Measurable disease must be outside of a prior radiation port
* Documented disease progression either during or after prior chemotherapy treatment
* No more than 2 prior chemotherapy regimens in the adjuvant or metastatic setting

  * Prior chemotherapy regimens must have contained a fluoropyrimidine (e.g., fluorouracil or capecitabine), oxaliplatin, and irinotecan

    * Patients who received no prior adjuvant therapy must have received 2 prior chemotherapy regimens for metastatic disease (e.g., FOLFOX followed by FOLFIRI)
    * Patients who received prior adjuvant therapy with a fluoropyrimidine plus oxaliplatin must have received no more than 1 chemotherapy regimen for metastatic disease that must have contained irinotecan
    * VEGF or EGFR inhibitors with prior chemotherapy allowed
* No known brain metastases
* Life expectancy \> 3 months
* ECOG performance status (PS) 0-2 or Karnofsky PS ≥ 60%
* WBC ≥ 3,000/mm³
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST/ALT ≤ 2.5 times ULN (5 times ULN with liver metastases)
* Creatinine normal or creatinine clearance ≥ 60 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No history of allergic reactions attributed to compounds of similar chemical or biological composition to dasatinib
* No QTc prolongation, defined as a QTc interval ≥ 480 msecs (Bazett correction)
* No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or active peptic ulcer disease) that would impair ability to swallow and retain dasatinib tablets

  * Prior partial colectomy is not considered an exclusion factor
* No clinically significant cardiovascular disease including any of the following:

  * Myocardial infarction or ventricular tachyarrhythmia within the past 6 months
  * New York Heart Association class II -IV congestive heart failure
  * Major conduction abnormality (unless a cardiac pacemaker is present)
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * History of significant bleeding disorder (including congenital \[e.g., von Willebrand's disease\] or acquired \[e.g., anti-factor VIII antibodies\] disorders)
  * Large pleural effusions
  * Psychiatric illness or social situations that would limit compliance with study requirements
* No currently active second malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix

  * Patients are not considered to have a currently active malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
* At least 4 weeks since prior radiation therapy and recovered
* No prior surgical procedures affecting absorption
* No prior treatment with inhibitors of src, PDGFR, KIT, or EPHA2
* More than 1 week since prior and no concurrent medications or substances that are potent inhibitors or inducers of CYP3A4
* More than 1 week since prior and no concurrent medications that inhibit platelet function (e.g., aspirin, dipyridamole, epoprostenol, eptifibatide, clopidogrel, cilostazol, abciximab, ticlopidine, or any non-steroidal anti-inflammatory drug)
* More than 1 week since prior and no concurrent agents that are generally accepted to have a risk of causing Torsades de Pointes, including quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine
* No concurrent anticoagulants (e.g., warfarin, heparin/low molecular weight heparin \[e.g., danaparoid, dalteparin, tinzaparin, or enoxaparin\])
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No concurrent grapefruit or grapefruit juice
* No other concurrent investigational agents or commercial agents or therapies