Primary Outcome Measures:
- To determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors [ Time Frame: Anticipated completion date December 2008 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- To determine the objective response rate and overall survival in patients enrolled in the study [ Time Frame: Anticipated completion date December 2008 ] [ Designated as safety issue: No ]
- To evaluate tissue biomarkers that relate to EGFR and Src signaling pathways on baseline tumor tissue and to study their modulation with cetuximab/dasatinib on post-treatment tumor tissue [ Time Frame: Anticipated completion date December 2008 ] [ Designated as safety issue: No ]
- To measure Src in peripheral blood mononuclear cells (PBMCs) before and after therapy [ Time Frame: Anticipated completion date December 2008 ] [ Designated as safety issue: No ]
- To evaluate EGFR gene copy number by FISH on baseline tumor tissue [ Time Frame: Anticipated completion date December 2008 ] [ Designated as safety issue: No ]
- To determine pharmacokinetic parameters of dasatinib in patients with and without feeding tubes [ Time Frame: Anticipated completion date December 2008 ] [ Designated as safety issue: No ]
Intervention Details:
Drug: Dasatinib (BMS-354825)
100 mg, 150 mg, or 200 mg per dose escalation schedule; continuous oral dosing on Days 1-21 of each 21-day cycle until progression or unacceptable toxicity develops.
Drug: Cetuximab (Erbitux, C225)
Loading dose of IV 400 mg/m^2 on Day 1 of Cycle 1; IV 250 mg/m^2 weekly thereafter each 21-day cycle until progression or unacceptable toxicity develops.
This is an open-label, phase I study of cetuximab and differing dose levels of dasatinib in adult patients with advanced solid malignancies. Cetuximab will be administered as an intravenous infusion on a standard dose and schedule (weekly, with the first dose at 400 mg/m2 and all subsequent weekly doses at 250 mg/m2). Dasatinib will be administered orally on a continuous schedule at the following dose levels: 100 mg QD (once a day), 150 mg QD, and 200 mg QD. Three to six patients will be enrolled at each dose level, and the final recommended phase II cohort will be expanded to include up to 12 additional patients. The doses will be escalated in successive cohorts of patients. On cycle 1, dasatinib administration will start one day prior to cetuximab administration. One cycle will be defined as 21 days, and cycles will continue until progression of disease or intolerable toxicities occur. Peripheral blood samples and pharmacokinetic blood samples will be taken on days 0, 1, 15, and 16 of Cycle 1 only. In patients with accessible tumor that give consent, patients will undergo a baseline tumor biopsy and a repeat biopsy after 14-21 days of the first cycle.