RO4929097 in Treating Patients With Metastatic Colorectal Cancer

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed colorectal cancer (NOS 10010029) with evidence of stage 4 disease (distant metastases)
* 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 for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan
* Patients must have received at least two prior lines of treatment in the metastatic setting; patients must have received 5-Fluorouracil (5-FU) or capecitabine, oxaliplatin and irinotecan, either in the adjuvant or metastatic setting; at least 4 weeks must have elapsed since prior chemotherapy or radiation therapy (6 weeks if the last regimen included mitomycin C)
* Life expectancy of greater than 3 months
* ECOG performance status =\<2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,000/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 9 g/dL
* Total bilirubin =\< 1.5 x institutional upper limit of normal
* AST(SGOT)/ALT(SGPT) =\< 2.5 x institutional upper limit of normal (or =\< 5 x institutional upper limit of normal in patients with liver metastases)
* Creatinine =\< 1.5 x institutional upper limit of normal
* The effects of RO4929097 on the developing human fetus at the recommended therapeutic dose are unknown; Notch signal pathway inhibitors are known to cause interruption of the embryonic signaling pathway and may lead to serious or life-threatening birth defects, including brain deformities, facial malformation, heart problems, or abnormal organs; therefore, women of childbearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 3 months post-treatment; should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study and for 3 months after study participation, the patient should inform the treating physician immediately
* Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior to the first dose of RO4929097 (serum or urine); a pregnancy test (serum) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study; prior to dispensing RO4929097, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the potential of RO4929097 to cause serious or life-threatening birth defects; female patients of childbearing potential are defined as follows:

  * Patients with regular menses
  * Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding
  * Women who have had tubal ligation
* Female patients may be considered to NOT be of childbearing potential for the following reasons:

  * The patient has undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy or bilateral oophorectomy
  * The patient is medically confirmed to be menopausal (no menstrual period) for 24 consecutive months
* 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 mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
* Patients may not be receiving any other investigational agents
* Patients with known brain or leptomeningeal 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
* Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible
* Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow tablets
* Known history of cirrhosis or clinically significant liver dysfunction
* Clinically significant hypocalcemia, hypomagnesemia or hypophosphatemia despite electrolyte supplementation
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia other than chronic, stable atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because RO4929097 is a Notch pathway inhibiting agent with the potential for serious or life-threatening birth defects or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with RO4929097, breastfeeding should be discontinued if the mother is treated with RO4929097; these potential risks may also apply to other agents used in this study
* HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with RO4929097; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
* Cardiovascular: baseline QTcF \> 450 msec (male) or QTcF \> 470 msec (female)
* Patients who have not recovered to \< CTCAE grade 2 toxicities related to prior therapy are not eligible to participate in this study