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.
- had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or
- received an investigational drug within 30 days or 5 half-lives (whichever is
- 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.