Background: Ix is a cytotoxic microtubule-stabilizing agent with anti-proliferative and anti-angiogenic properties. S is a multi-targeted receptor tyrosine kinase inhibitor. IX and S combination may be synergistic, since S may increase delivery of Ix to the tumor by inducing vascular normalization. Methods: Patients (pts) with advanced STs were enrolled in a phase I, dose-escalation study to assess safety, pharmacokinetics (PK), angiogenesis biomarkers and to determine the recommended phase II dose. Eligibility: age > 18, ≤ 4 prior systemic therapies (tx), ECOG PS 0-2, measurable/evaluable disease and good organ function. Treatment schedules: A (weekly Ix, 3 out of 4-weeks): starting dose 7.5 mg/m² IV (1A), 15 mg/m² IV (2A) and 20 mg/m² IV (3A). Schedule B (every 3 weeks): starting dose 20 mg/m² IV (1B), 30 mg/m² IV (2B) and 40 mg/m² IV (3B). In both schedules, S was given continuously starting on day 8 of cycle 1 at 37.5 mg PO daily. A standard 3 + 3 design was used and dose-limiting toxicities (DLTs) assessed in the first cycle. Results: 30 patients were enrolled. Two pts withdrew before starting tx. Baseline characteristics: median age: 61.5 (25-78); males/females: 19/9; most frequent STs: colorectal -CRC- (16), pancreas (2), prostate (2); median PS: 1; median of prior tx: 3. Number of pts evaluable for toxicity/dose escalation/efficacy: 28/23/21. One DLT was observed in schedule 3A (grade (gr) 3 DVT) and 2 in schedule 3B (gr 4 mucositis/gr 3 dehydration; gr4 neutropenia). Other gr 3 /4 AEs (non DLTs): leukopenia (18%), neutropenia (25%), lymphopenia (21%), anemia (14%), thrombocytopenia (7%), leukocytosis (4%), fatigue (25%), neuropathy (7%), mucositis (7%), nausea (7%), vomiting (4%), hyperglycemia (4%), syncope (4%), abdominal pain (4%) and GI bleed (4%). Median # of cycles (evaluable pts): 3 (range1-10). Three pts achieved PR (2 with CRC). Eight patients had SD (5 with CRC). 10 patients had PD. Conclusions: The combination of Ix and S appears to have acceptable toxicity and encouraging activity in heavily pretreated pts. The recommended phase II dose for S is 37.5 mg po daily with Ix 20 mg/m² in Schedule A and Ix 30 mg/m² in schedule B. Angiogenesis biomarkers and PK analyses are underway.