Open-label Study of Topotecan and Pazopanib in Advanced Solid Tumors

A Phase I Open-label Study of the Safety, Tolerability, and Pharmacokinetics of Two Schedules of Oral Topotecan in Combination With Pazopanib in Subjects With Advanced Solid Tumors

To determined what dose of topotecan can be safely given with daily pazopanib.

A Phase I Open-label Study of the Safety, Tolerability, and Pharmacokinetics of Two Schedules of Oral Topotecan in combination with Pazopanib in Subjects with Advanced Solid Tumors

Inclusion Criteria -

• signed, written informed consent.
• at least 18 years of age.
• ECOG performance status 0 or 1.
• Subjects must have histologically or cytologically confirmed diagnosis of advanced cancer and a solid tumor malignancy that has relapsed or is refractory to standard therapy or for which there is no established therapy.
• able to swallow and retain oral medications.
• females are eligible to enter and participate in this study providing adequate established contraception is being practiced.

Exclusion Criteria

• had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)
• received an investigational drug within 30 days or 5 half-lives (whichever is longer).
• received prior treatment with pazopanib/investigational anti-angiogenic compounds.
• presence of uncontrolled infection.
• pregnant or lactating.
• poorly controlled hypertension (SBP of ? 140 mmHg, or DBP of ? 90 mmHg.
• Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.-
• arterial thrombi, myocardial infarction, admission for unstable angina, uncontrolled or symptomatic arrhythmia, cardiac angioplasty, or stenting within the last 6 months.
• any unresolved bowel obstruction or diarrhea ? Grade 1.
• received an allogeneic bone marrow transplant.
• known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or topotecan.
• any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study.
• psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
• clinical history, current alcohol or illicit drug use which, in the judgment of the investigator, would interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations.