This phase 0 trial is studying whether 2 weeks of cetuximab and dasatinib will change tumor cells in patients with colorectal cancer and liver metastases that can be removed by surgery. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the biological effects of cetuximab, dasatinib, or the combination on epidermal growth factor receptor (EGFR)- and Src-signaling pathways in resected colorectal cancer liver metastases.

OUTLINE: This is a multicenter study. Patients are initially enrolled in cohort A. Once cohort A is completed, additional patients are enrolled and randomized to treatment in either cohorts B or C. If a significant biological effect is seen in cohorts B or C, additional patients are enrolled in cohort D.

COHORT A: Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy.

COHORT B: Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m^2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15.

COHORT C: Patients receive dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15.

COHORT D: Patients receive 400 mg/m^2 cetuximab IV over 120 minutes on day 1 and 250 mg/m^2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15.

Patients undergo tumor tissue (from initial liver tumor biopsies and liver resection samples), serum, and peripheral blood mononuclear cell sample collection periodically for biomarker analysis via immunohistochemistry (IHC).

Inclusion Criteria:

• Patients must have histologically confirmed adenocarcinoma arising from the large intestine that has metastasized to the liver; liver metastases may be synchronous or metachronous
• The liver metastases must be considered surgically resectable prior to the initiation of study drugs
• Prior chemotherapy or chemoradiotherapy for colorectal cancer is allowed provided that toxicities from prior therapy have resolved to Grade 1 or less; no prior anti-EGFR or anti-Src therapy is allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Absolute neutrophil count >= 1.5 x 10^9/L
• Hemoglobin ≥ 9.0 Gm/dL
• Platelets >= 100 x 10^9/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine transaminase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 5 x institutional upper limit of normal
• Creatinine =< 1.5 institutional ULN
• Women must have a negative pregnancy test; 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 and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Although KRAS status will be evaluated in the tumor, wild type KRAS status is not an eligibility criterion

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or 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 receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab or dasatinib
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cetuximab or dasatinib, breastfeeding should be discontinued if the mother is treated with cetuximab or dasatinib
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with cetuximab or dasatinib; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
• Patients on potent CYP3A4 inducers and inhibitors