Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer

Inclusion Criteria

• •Patients must have histologically or cytologically confirmed metastatic colorectal adenocarcinoma
• •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) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan
• •Patients must have received at least one prior therapy for metastatic disease; prior therapy with anti-EGFR antibody is allowed only as long as patient did not require dose reductions of the anti-EGFR antibody because of poor tolerability
• •Life expectancy of greater than 3 months
• •ECOG performance status =\<2 (Karnofsky \>= 60%)
• •Leukocytes \>= 3,000/mcL
• •Absolute neutrophil count \>= 1,500/mcL
• •Platelets \>= 100,000/mcL
• •Hemoglobin \>= 9 g/dL
• •Total bilirubin within normal institutional limits if no liver metastases
• •Total bilirubin \< 1.5 X the institutional upper limit of normal if liver metastases are present
• •AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal if no liver metastases
• •AST(SGOT)/ALT(SGPT) \< 5 X institutional upper limit of normal if liver metastases are present
• •Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• •For the phase I dose expansion, tumor must be KRAS wildtype
• •There must be available a tumor block or 20 unstained slides for correlative studies
• •The effects of RO4929097on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because Notch signal pathway inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, 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 12 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 12 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 or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of RO4929097; a positive urine test must be confirmed by a serum pregnancy test; 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 teratogenic potential of RO4929097
• •* 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
• •Ability to swallow pills