Combination Chemotherapy and Bevacizumab With or Without RO4929097 in Treating Patients With Metastatic Colorectal Cancer

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the colon or adenocarcinoma of the rectum * Metastatic disease by imaging * Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20mm by conventional techniques or as ≥ 10 mm by spiral CT scan * No known brain metastases * ECOG performance status 0-1 * ANC ≥ 1,500/mm³ * WBC ≥ 3,000/mm³ * Platelet count ≥ 100,000/mm³ (without a platelet transfusion ≤ 14 days prior to study) * Hemoglobin ≥ 9 g/dL * Serum creatinine ≤ 1.5 times upper limit of normal (ULN) * Urine protein:creatinine ≤ 0.5 or proteinuria \< 1,000 mg on 24-hour urine collection * Total bilirubin ≤ 1.5 times ULN * AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN for patients with liver metastases) * Albumin ≥ 2.5 g/dL * Amylase ≤ 2 times ULN * Lipase ≤ 2 times ULN * PTT ≤ 1.2 times ULN * INR ≤ 1.2 times ULN * No patients with uncontrolled hypophosphatemia, hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as less than the lower limit of normal for the institution, despite adequateelectrolyte supplementation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use two forms of contraception (i.e., barrier contraception and one other method of contraception) prior to, during, and for ≥ 12 months after study participation * Patients must not have current evidence of or history of another malignancy except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other curatively treated solid tumors with no evidence of disease for ≥ 3 years prior to enrollment * Able to swallow capsules * No malabsorption syndrome or other condition that would interfere with intestinal absorption * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 used in the study * No clinically important history of liver disease, including known viral, other hepatitis, or cirrhosis * No uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * A history of torsades de pointes or other significant cardiac arrhythmias * Psychiatric illness and/or social situations that would limit compliance with study requirements * No baseline QTcF \> 450 msec (male) or QTcF \> 470msec (female) * No serious or non-healing wound, ulcer, or bone fracture * No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No significant traumatic injury within the past 28 days * No clinically significant cardiovascular disease, including any of the following: * Inadequately controlled hypertension (systolic BP \> 160 mm Hg and/or diastolic BP \> 90 mm Hg despite antihypertension medication) * History of cerebrovascular accident within the past 6 months * Myocardial infarction or unstable angina within the past 6 months * NYHA grade II-IV congestive heart failure * Serious and inadequately controlled cardiac arrhythmia * No requirement for antiarrhythmics or other medications known to prolong QTc * No significant vascular disease (e.g., aortic aneurysm, requiring surgical repair, history of aortic dissection, or recent peripheral arterial thrombosis) within the past 6 months * No clinically significant peripheral vascular disease * No evidence of bleeding diathesis or coagulopathy * No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies * Recovered to \< NCI CTCAE grade 2 toxicities related to prior therapy * No prior adjuvant or neoadjuvant chemotherapy for colorectal cancers within 12 months of development of metastases * No prior chemotherapy or gamma-secretase inhibitors or other investigational agents for metastatic colorectal cancer * No prior radiotherapy for colorectal cancers including in the neoadjuvant or adjuvant setting within 12 months of development of metastases * No major surgical procedure or open biopsy within the past 28 days and no anticipation of need for major surgical procedures during the course of the study * No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) * Patients who switch from warfarin sodium to alternative anti-coagulant agents allowed * No concurrent medications that are strong inducers, inhibitors, or substrates of CYP3A4, including ketoconazole and grapefruit juice * No concurrent combination antiretroviral therapy for HIV-positive patients