A Phase I/II Study of Gleevec® Combined With Panitumumab (Vectibix®) in Patients Prescreened for C-kit/PDGFr Activated Pathways Using a Proteomic Based Assay
- 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
- 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.
- 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
- 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.