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,