AZD0530 (NSC 735464) in Treating Patients With Previously Treated Metastatic Colon Cancer or Rectal Cancer

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic
* Patients must have measurable disease, defined (per RECIST criteria) 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 \>= 10 mm with spiral CT scan
* Patients must have received one and only one prior chemotherapy regimen for metastatic colorectal cancer; patients may have received biologic therapy (e.g., bevacizumab) in combination with chemotherapy as part of their prior chemotherapy
* ECOG performance status 0-2
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 9 g/dL
* Total bilirubin =\< 1.5 x institutional ULN
* AST(SGOT)/ALT(SGPT) =\< 3.0 x institutional ULN
* Creatinine within normal institutional limits OR estimated CrCl (Cockcroft-Gault) or 24 hr urine collection of \>= 50 mL/min
* The effects of AZD0530 on the developing human fetus at the recommended therapeutic dose are unknown; however, AZD0530 has been shown to cause gross fetal malformations and to negatively impact embryo fetal survival in rats; for this reason and because many tyrosine kinase inhibitors are known to be teratogenic, 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, for the duration of study participation, and up to 30 days following removal from the study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; women of child-bearing potential will have serum beta-Hcg levels drawn up to 7 days prior to receiving study treatment
* Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD0530, breastfeeding should be discontinued if the mother is treated with AZD0530
* 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 study registration or those who have not recovered from treatment related adverse events \> grade 1 (except for neuropathy \[ies\] which may be =\< grade 2) due to agents administered more than 4 weeks earlier
* Use of specifically prohibited CYP3A4-active agents or substances are not permitted during protocol treatment, and patients who must continue treatment with these agents are not eligible; prohibited drugs should be discontinued seven (7) days or 5 half-lives (whichever is the longer time period) prior to the administration of the first dose of AZD0530 and for 7 days or 5 half-lives (which ever is the longer time period) following discontinuation of AZD0530
* Patients may not be receiving any other investigational agents
* Patients with greater than +1 proteinuria on two consecutive readings taken no less than 24 hours apart are ineligible
* Patients with QTc prolongation (defined as a QTc interval greater than or equal to 480 msecs) are ineligible
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring parenteral antibiotics at the time of registration), cardiac disease NYHA class III or IV, unstable angina pectoris, unstable cardiac arrhythmia or tachycardia (heart rate \>= 100 beats per minute), poorly controlled hypertension (systolic blood pressure \>= 140 mmHg or diastolic blood pressure \>= 90 mmHg)
* Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow AZD0530 tablets are excluded
* 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
* Pregnant women are excluded from this study because AZD0530 has the potential for teratogenic or abortifacient effects as shown by the gross fetal malformation and effects on embryofetal survival seen in reproductive toxicity studies in the rat
* Patients with a history of another primary malignancy within the last 5 years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix
* Patient who are known to be HIV-positive are ineligible because of the potential for pharmacokinetic interactions with AZD0530 and antiretroviral therapy (HAART)