A phase I study of the combination of daily oral pazopanib with intravenous ifosfamide in patients with advanced solid malignancies.

1. Subjects must provide written informed consent prior to performance of study
specific procedures or assessments, and must be willing to comply with treatment
and follow up assessments and procedures;

2. Histologically or cytologically confirmed diagnosis of advanced solid tumor for
which ifosfamide-based systemic therapy is considered appropriate or for which
there is no standard therapy;

3. Age >18 years;

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

5. Adequate organ function;

6. There must be measurable disease or evaluable disease (according to RECIST v1.1
criteria) for subjects to be included in the cohort expansion phase. Measurable
disease is not a criterion for subjects enrolling in the dose escalation phase;

7. Able to swallow and retain oral medication;

8. A life expectancy of at least 12 weeks.

1. Unable to discontinue prohibited medications, as listed in Section 5.5.2, 14 days or
five half-lives (whichever is longer) of the drug prior to Visit 1 and for the duration
of the study;

2. Clinically significant gastrointestinal abnormalities which might interfere with oral
dosing;

3. Any unstable or serious concurrent condition (e.g., active infection requiring
systemic therapy);

4. Poorly controlled hypertension (SBP of ³160 mmHg, or DBP of ³90 mmHg).
Note: Initiation or adjustment of blood pressure medication is permitted prior to
study entry provided the subject has 2 consecutive blood pressure readings less than
160/90 mmHg, each separated by a minimum of 1 hour. These readings need to be
collected prior to the first dose. See Appendix 2 for details on blood pressure control
and reassessment prior to study enrollment;

5. Prolongation of corrected QT interval (QTc) >480 msecs;

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

A. Cardiac angioplasty or stenting;

B. Myocardial infarction;

C. Unstable angina;

D. Symptomatic peripheral vascular disease;

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

7. History of cerebrovascular accident, pulmonary embolism or untreated deep venous
thrombosis (DVT) within the past 6 months.
Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulant
agents (excluding therapeutic warfarin) for at least 6 weeks are eligible;

8. Macroscopic hematuria;

9. Hemoptysis that is clinically relevant within 4 weeks of first dose of study drug;

10. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer;

11. Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study
drug;

12. Biological therapy, hormonal therapy or treatment with an investigational agent
within 28 days (for bevacizumab, 60 days) prior to the first dose of study drug;

13. Has not recovered from toxicities associated with prior anti-cancer therapy;

14. Metastatic disease to the brain or leptomeninges (of note: radiologic assessment of
the brain is only needed in those subjects with clinical symptoms suspicious for brain
metastases);

15. Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol;

16. Clinically assessed as having inadequate venous access for PK sampling;

17. Is pregnant or lactating.
Note: Female subjects who are lactating should discontinue nursing prior to the first
dose of study drug and should refrain from nursing throughout the treatment period
and for 14 days following the last dose of study drug.