The purpose of this study is to evaluate the safety and tolerability of imatinib mesylate in combination with panitumumab for the treatment of stage IV colorectal cancer that has spread to the liver. It will also assess the whether imatinib mesylate, either alone or in combination with panitumumab, is effective in treating this type of cancer. In addition, the study will evaluate the feasibility of a predefined lab score and whether it can predict which patients will respond to treatment with imatinib mesylate.

Recently, a series of clinical trial outcome reports have shown that KRAS mutations (and to a lesser extent KRAS mutations with BRAF V600E mutation) significantly negatively correlate with response to anti-epidermal growth factor (EGFR) mAbs, such as panitumumab, in metastatic colorectal cancer (mCRC) patients. WT KRAS status was shown to be required but not sufficient to confer sensitivity to panitumumab monotherapy. The molecular mechanisms underlying the response or lack of response to EGFR-directed therapies in CRC patients with WT RAS status are unknown. Potential mechanisms of response include activation of EGFR through receptor mutation or autocrine/paracrine ligand binding, activation while tumors that do not respond to EGFR-directed therapy may have activation of other distinct pathways such as VEGF, PDGF, and insulin-like growth factor 1 receptor; activating mutations of additional signaling proteins downstream of EGFR such as PI3K, and Src, or downstream of KRAS, such as RAF; and loss of function genes such as phosphatase and tensin homolog (PTEN). Identifying prognostic and predictive biomarkers to EGFR-directed therapy will prove important for the selection of therapeutic combinations to maximize clinical benefit. In addition to ascertaining resistance mechanisms other biomarkers such as EGFR gene copy number and expression levels of EGFR ligands in tumor cells may be useful to further refine responder population. The current approach applies to the panitumumab monotherapy and indicates that KRAS status should be considered when selecting mCRC patients as candidates for treatment. Thus, patients who are found to harbor KRAS mutation(s) as identified in the pre-treatment liver biopsy specimen will not be eligible for continuation on the trial, but following patient consent, the pre-treatment biopsy will be studied for pathway activation analysis by a CAP/CLIA compliant independent laboratory for research purposes only in the hopes for generating future hypothesis on pathway activation correlating with KRAS mutation status and help extend research into predictive pathway biomarkers for anti-EGFR therapy.

This is a two arm prospective non-randomized study that is designed to assess the safety and efficacy of Gleevec and Vectibix in the treatment of metastatic colorectal cancer to the liver. It also studies the change in phosphorylation levels of Gleevec® targets (PGDT) and tumor burden in patients treated with Gleevec® monotherapy followed by Gleevec® + Vectibix® combination therapy versus treatment with standard of care (panitumumab).

Inclusion Criteria:

• Patients ≥ 18 years of age.
• Histologically documented diagnosis of Stage IV Metastatic Colorectal Cancer with Liver Metastases, refractory or progressive after at least one (1) prior line of therapy that must include a fluoropyrimidine (5-fluorouracil or capecitabine) AND (oxaliplatin OR irinotecan), i.e. FOLFOX, FOLFIRI, XELOX, or XELIRI.
• Documentation of wild type k-Ras expression in the liver lesion.
• At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 3), or other response assessment criteria, as appropriate.
• Must have ≥ 1 measurable liver lesion that can be accessed by CT guided biopsy.
• Performance status 0,1, or 2 (ECOG).
• Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL, creatinine < 1.5 x ULN, ANC > 1.5 x 10^9/L, platelets > 100 x 10^9/L.
• Life expectancy of at least 3 months.
• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.
• Written, voluntary informed consent.

Exclusion Criteria:

• Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
• Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
• Female patients who are pregnant or breast-feeding.
• Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
• Patient has a known brain metastasis not treated with definitive therapy with stable disease ≥ 4 weeks.
• Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient received chemotherapy within 2 weeks (6 weeks for nitrosourea or mitomycin-C)prior to study entry, unless the disease is rapidly progressing.
• Patient previously received radiotherapy to ≥ 25% of the bone marrow
• Patient had a major surgery within 2 weeks prior to study entry.
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
• Patients intolerant to imatinib mesylate.

Any serious adverse event occurring after the patient has provided informed consent, has started taking the study medication, and until 4 weeks after the patient has stopped study participation.

Note that the subject randomized to the standard of care arm withdrew after randomization, so adverse event data is not available.

This is a pilot study utilizing only a small sample size of people.