Feasibility Study of Pazopanib in Combination With Chemotherapy in Gynaecological Tumors

Inclusion criteria: * Inclusion Criteria * A subject will be considered eligible for inclusion in this study only if all of the following criteria are met: * Subjects must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up. * Procedures conducted as a part of routine clinical management of the subject (e.g., blood count, imaging study) and obtained prior to signed informed consent may be utilized for Screening or Baseline purposes provided these tests are obtained as specified in the protocol). * Female subjects ≥18 years of age with newly diagnosed advanced gynaecological malignancies for whom carboplatin and paclitaxel based chemotherapy is indicated. Patients may have surgery to debulk or resect disease but may not have received chemotherapy or radiotherapy. * Histological confirmation of the following: epithelial ovarian cancer, endometrial carcinoma, uterine sarcoma, mixed Müllerian tumour, fallopian tube carcinoma, primary peritoneal carcinoma, cervical carcinoma or vulvar carcinoma. * Performance status must be ECOG 0 1. * Adequate organ system function as defined in Table 6 * Table 6 Definitions for Adequate Organ Function * System (Laboratory Values) * Hematologic: * Absolute neutrophil count (ANC) (≥ 1.5 X 109/L) * Hemoglobin1 (≥9 g/dL) * Platelets (≥100 X 109/L) * International normalized ratio (INR)(≤ 1.2 X upper limit of normal (ULN)) * Partial thromboplastin time (PTT) (≤1.2 X ULN) * Hepatic: p Total bilirubin (≤1.5 X upper limit of normal (ULN)) * AST and ALT (≤ 2.5 X ULN) * Renal: * Serum Creatinine (≤ 1.5 mg/dL) * Or, if serum creatinine \>1.5 mg/dL, (≥ 50 mL/min) * Calculated creatinine clearance * Urine Protein to Creatinine Ratio2 (\<1) * Patients may not have had a transfusion within 7 days of screening assessment. * If UPC ≥1, then a 24-hour urine protein must be assessed. Patients must have a 24-hour urine protein value \<1g to be eligible. * Measurable or non-measurable disease. * A female subject is eligible to enter and participate in the study if she is: * Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who: * Has had a hysterectomy, or * Has had a bilateral oophorectomy (ovariectomy), or * Has had a bilateral tubal ligation, or * Is post-menopausal * Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value \>40 mIU/mL and an estradiol value \< 40pg/mL (\<140 pmol/L). * Subjects who are using hormone replacement therapy and whose menopausal status is in doubt will be required to use a highly effective method of contraception (as outlined in this inclusion criterion) if they wish to continue their HRT during the study. Otherwise, these subjects must discontinue HRT prior to study enrollment to allow confirmation of post menopausal status. For most forms of HRT, at least 2-4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. Following confirmation of post menopausal status, these subjects can resume HRT during the study without use of contraception. * Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow: * An intrauterine device with a documented failure rate of less than 1% per year. * Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female. * Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product. * Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide). Note: Oral contraceptives are not reliable due to potential drug-drug interactions. * Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug. * Recovered from the effects of surgery. * Prior radiotherapy is permissible, provided at least 4 weeks have elapsed since the last treatment to allow for full bone marrow recovery. Exclusion Criteria * A subject will not be eligible for inclusion in this study if any of the following criteria apply: * Prior use of anticancer therapy (except cytoreductive surgery \[debulking\]) for their cancer. * Presence of bulky, residual, squamous cell tumors. * Is unable to discontinue prohibited medications, as listed in Section 8.2 for 14 days or five half-lives of a drug prior to Visit 1 and for the duration of the study. * Clinically significant gastrointestinal abnormalities which might interfere with oral dosing, including but not limited to: * Malabsorption syndrome * Major resection of the stomach or small bowel that could affect the absorption of study drug * Active peptic ulcer disease * Inflammatory bowel disease * Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment. * Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy). * Inadequately controlled hypertension (systolic blood pressure \[SBP\] of ≥140 mmHg, or diastolic blood pressure \[DBP\] of ≥ 90 mmHg). Initiation or adjustment of blood pressure medication is permitted prior to study entry provided the subject has 2 consecutive blood pressure readings less than 140/90 mmHg, each separated by a minimum of 24 hours. These readings need to be collected prior to the first dose. * Hemoptysis within four weeks prior to first dose of study drug. * Prior major trauma within 14 days prior to first dose of study drug. * Prior major surgery within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. In the case of surgery involving the bowel, subjects must be 28 days post-surgery to be eligible. * Prolongation of corrected QT interval (QTc) \> 480 msecs. * History of any one of more of the following cardiovascular conditions within the past 6 months: * Cardiac angioplasty or stenting * Myocardial infarction * Unstable angina * Symptomatic peripheral vascular disease * Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA) \[See History of cerebrovascular accident (CVA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. * Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible. * Metastatic disease to the brain or leptomeninges.