Study of Pazopanib and Ixabepilone in Patients With Solid Tumors

Treatment with ixabepilone will be given at an assigned dose as a 3 hour intravenous infusion
on day 1 of a 21 day cycle. Treatment with pazopanib will be given at an assigned dose by
mouth once a day, beginning on day 1 and continuing daily. Disease assessment will be done
every 2 cycles (6 weeks) with treatment continuing until disease progression, unacceptable
toxicity or patient refusal.

Inclusion Criteria:

- Diagnosis of advanced non-hematologic solid tumor malignancy, including, but not
limited to breast, lung, colon, pancreatic, head and neck, kidney or sarcoma that has
failed or become intolerant to standard therapy and is no longer likely to respond to
such therapy Effective with the August 2011 version of the protocol, enrollment is
limited to squamous cell carcinoma of the head and neck (refer to section 1.4 for
rationale). Note: Patients with a primary diagnosis of hepatocellular carcinoma will
be eligible for enrollment into dose level 1 or 2 only, provided they met all other
inclusion/exclusion criteria - the maximum tolerated dose (MTD) for pazopanib
monotherapy in patients with hepatocellular cancer was found to be 600 mg daily.

- Measureable or evaluable disease per Response Evaluation Criteria in Solid Tumors
(RECIST).

- Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed; however
prior use of either pazopanib or ixabepilone alone or in combination is not allowed.

- At least 14 days must have elapsed since 1) previous systemic therapy (28 days for
bevacizumab) before the 1st dose of study drug, 2) last dose of radiation therapy or
surgery (28 days for major surgery).

- Patient must have recovered from the acute toxic effects of previous anti-cancer
treatment prior to study enrollment.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

- Adequate organ function within 14 days of enrollment defined as:

- Absolute neutrophil count (ANC) >1.5 x 10^9/L

- Hemoglobin > or = 9 g/dL

- Platelets > or = 100 x 10^9/L

- Prothrombin time or international normalized ratio, and partial thromboplastin
time (PTT) < or = 1.2 x upper limit of normal (ULN)

- Total bilirubin < or = ULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < or = 2.5 x
ULN

- Serum creatinine < or = 1.5 mg/dL

- Urine protein to Creatinine Ratio < 1

- Total serum calcium < 12.0 mg/dL

- Men and women with child-bearing potential must adhere to protocol criteria to prevent
conception during study

Exclusion Criteria:

- Women who are pregnant or nursing.

- Prior radiation to > =or = 30% of major bone marrow containing areas (pelvis, lumbar
spine)

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis

- Clinically significant gastrointestinal abnormalities that may increase the risk of GI
bleeding or may affect absorption of investigational product

- History of another malignancy - must be at least 3 years disease-free

- Presence of uncontrolled infection

- Prolongation of corrected QT interval (QTc) > 480 msecs

- History of any one or more of the following cardiovascular conditions within the past
6 months:

- Cardiac angioplasty or stenting

- Myocardial infarction

- Unstable angina

- Coronary artery bypass graft surgery

- Symptomatic peripheral vascular disease

- Class III or IV congestive heart failure, as defined by the New York Heart
Association (NYHA)

- Poorly controlled hypertension

- History of cerebrovascular accident,pulmonary embolism or untreated deep venous
thrombosis (DVT) within the past 6 months

- Prior major surgery or trauma within 28 days prior to 1st dose of study drug

- Evidence of active bleeding or bleeding diathesis

- Known endobronchial lesions or involvement of large pulmonary vessels by tumor

- Hemoptysis with 6 weeks of 1st dose of study drug

- Neuropathy Grade 1