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

Inclusion criteria

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• 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.