Linifanib in Treating Patients With Advanced, Refractory Colorectal Cancer

Inclusion Criteria:

* Histologically confirmed colorectal cancer refractory to at least 1 but no more than 3 systemic chemotherapy regimens
* Patients must have received one standard chemotherapy regimen in the metastatic setting
* Established Ras-mutant tumor status (archived specimens are okay and this test can have been performed at local laboratories)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* The subject must have adequate bone marrow and organ function, defined as follows:
* Hemoglobin ≥ 9g/dL
* Platelets \>100,000,
* Absolute neutrophil count (ANC) \> 1000/uL,
* Serum creatinine \< 1.5 x upper limit of normal,
* Total bilirubin \< 1.5 x the upper limit of normal,
* AST and ALT ≤ 2.0 x upper limit of normal (or ≤ 5 x ULN in the presence of liver metastases)
* Measurable disease, defined as at least 1 unidimensionally measurable lesion on a computed tomography (CT) scan or magnetic resonance imaging (MRI) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days of study treatment; surgically sterile and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-child-bearing potential
* Female subjects of child-bearing potential and male subjects must agree to use adequate contraception prior to study entry, for the duration of study participation and up to two months after the last dose of ABT 869; adequate contraception methods should be used consistently and correctly and include the following:
* Total abstinence from sexual intercourse (minimum one complete menstrual cycle)
* A vasectomized partner
* Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
* Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
* The subject must be willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations
* The subject must have given written informed consent prior to the initiation of any screening or study-specific procedures
* Ability to understand and the willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study-specific procedures
* Patients must be at least 14 days status post last day of prior chemotherapy (at least 28 days since last dose of bevacizumab) and have recovered to grade =\< 1 from all chemotherapy-associated side effects
* Patients must have the ability to swallow pills

Exclusion Criteria:

* Untreated central nervous system (CNS) metastases; patients may have CNS metastases from any timeframe as long as they are treated and not progressing; brain imaging is not required if there is no clinical suspicion of brain metastases
* Pregnant or lactating females are excluded
* Uncontrolled hypertension defined as systolic blood pressure (BP) \> 140 and/or diastolic BP \> 90 initially evaluated on day of study eligibility determination (when laboratory parameters are assessed), but must be maintained on day of study initiation; (If a patient is found to have a value outside the range above, repeat BP may be assessed and if at subsequent readings x 2 (taken in clinic at least 15 minutes apart) criteria are met, the patient can then be eligible; initiation or modification of antihypertensives is allowed to achieve adequate BP for eligibility; finally, in the case that subsequent determinations are required, the BP assessment that counts towards eligibility is the reading on the day of study initiation); (note: a clinic BP reading without the patient having been at rest for 15 minutes or with the wrong cuff size can be repeated the same day for eligibility criteria to be determined
* Active bleeding or history of bleeding from cancer related events
* History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) or recent myocardial infarction (MI) (\< 6 months)
* Active ulcerative colitis, Crohn's disease or Celiac disease that could interfere with the absorption of the drug
* Current use of therapeutic anticoagulation; low dose anticoagulation for catheter prophylaxis is permitted; Lovenox is permitted for prophylaxis; (Note: patients who develop thrombosis and are placed on anticoagulation while on this trial may continue on study at the discretion of the investigator)
* The subject has had major surgery within 28 days of Study Day 1
* The subject has had radiation therapy within 14 days of Study Day 1
* The subject had prior bevacizumab within 28 days of study day 1
* No prior treatment with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors; prior treatment with other investigational agents is allowed
* The subject has a medical condition, which in the opinion of the study investigator, places them at unacceptably high risk for toxicities
* Other active malignancy for which the patient has been treated within the past one year
* Subjects with known human immunodeficiency virus (HIV) infection are excluded
* Subject has documented left ventricular ejection fraction (LVEF) \< 50%
* Subject has Proteinuria \> grade 1 at baseline measured by urine dipstick (2+ or greater) and confirmed by 24 hour (hr) urine collection (\> = 1g/24hrs)