Phase I Trial of Oral Metronomic Topotecan and Oral Pazopanib to Treat Recurrent/Persistent Gynecologic Tumors

Inclusion Criteria

• Subjects must provide written informed consent prior to the performance of study specific procedures, and must be willing to comply with treatment and follow-up.
• Female patients, greater than 18 years of age with a histologically confirmed recurrent/persistent gynecologic malignancy.
• For patients with recurrent/persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: persistent disease = progression during primary platinum therapy; recurrent disease = disease that recurs ≤ 12 months after discontinuing primary platinum therapy; if disease recurrence occurs > 12 months after discontinuing primary platinum therapy, there must be progression either during a 2nd platinum therapy or 9.0 g/dL.
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.
• Platelet count ≥ 100 x 10^9/L.
• Prothrombin time (PT) or international normalized ratio (INR) 50 mL/min
• Urine dipstick for protein 480 milliseconds.
• 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
• Symptomatic peripheral vascular disease
• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• Poorly controlled hypertension (defined as systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
• History of cerebrovascular accident, transient ischemic attack, pulmonary embolism, or insufficiently treated deep vein thrombosis (DVT) within the past 6 months. Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
• Evidence of active bleeding or bleeding diathesis.
• Recent hemoptysis in excess of 2.5 mL within 8 weeks of 1st dose of study treatment.
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
• Use of any prohibited medication within 14 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study treatment and during the study.
• Prior use of any investigational or licensed anti-angiogenic agent, including topotecan, bevacizumab, thalidomide, and agents that target vascular endothelial growth factor (VEGF), VEGF receptors, or platelet-derived growth factor (PDGF).
• Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia.
• Known hypersensitivity to topoisomerase I inhibitors or pazopanib.
• Administration of any non-oncologic investigational drug within 30 days or five half-lives of a drug (whichever is longer) prior to the first dose of study treatment.