Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ)

Exclusion Criteria

• •prior malignancies; subject who have had another malignancy and have been disease-free for 5 years which effect progression free survival, or subject with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
• •History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) is required only if clinically indicated or if the subject has a history of CNS metastases.
• •clinically significant gastrointestinal abnormalities that might interfere with oral dosing or that may increase the risk for gastrointestinal bleeding
• •clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
• •Grade 3 or 4 diarrhoea
• •Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy)
• •poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg\]
• •Prolongation of corrected QT interval (QTc) \>450 milliseconds using Bazett's formula
• •History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting; myocardial infarction; unstable angina; symptomatic peripheral vascular disease; coronary artery by-pass graft surgery
• •Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
• •History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
• •Macroscopic hematuria
• •Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug
• •Evidence of active bleeding or bleeding diathesis
• •known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or involvement of large pulmonary vessels by tumor
• •prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
• •Chemotherapy or radiation therapy or tumour embolization within 2 weeks prior to the first dose of study drug
• •biological therapy, immunotherapy, hormonal therapy or treatment with an investigational agent within 14 days (for bevacizumab, 60 days) or 5 half-lives, whichever is longer prior to the first dose of study drug
• •is unable or unwilling to discontinue predefined prohibited medications listed in the protocol (refer to section 4.2.3) for 14 days or five half-lives of a drug (whichever is longer) prior to first dose of study drug and for the duration of the study
• •any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity, except alopecia
• •known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
• •psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
• •clinically assessed as having inadequate venous access for PK sampling
• •any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
• •legal incapacity or limited legal capacity
• •Participation in another clinical study with experimental therapy within the 30 days before start of treatment
• •Subjects housed in an institution on official or legal orders
• •Pregnancy or lactation period