previously untreated, advanced gynaecological tumors MedDRA version: 9.1 Level: LLT Classification code 10033128 Term: Ovarian cancer MedDRA version: 9.1 Level: LLT Classification code 10014743 Term: Endometrial carcinoma MedDRA version: 9.1 Level: LLT Classification code 10016180 Term: Fallopian tube cancer MedDRA version: 9.1 Level: LLT Classification code 10052171 Term: Peritoneal carcinoma MedDRA version: 9.1 Level: LLT Classification code 10051963 Term: Vulvar carcinoma MedDRA version
Conditions
Sponsors
GlaxoSmithkline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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). 2. 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. 3. 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. 4. Performance status must be ECOG 0 1. 5. Adequate organ system function as defined in Table 6 of the protocol 6. Measurable or non-measurable disease. 7. 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: a. Has had a hysterectomy, or b. Has had a bilateral oophorectomy (ovariectomy), or c. Has had a bilateral tubal ligation, or d. 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: a. An intrauterine device with a documented failure rate of less than 1% per year. b. Vasectomized partner who is sterile prior to the female subject’s entry and is the sole sexual partner for that female. c. 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. d. 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. F
Exclusion criteria
Exclusion criteria: 1. Prior use of anticancer therapy (except cytoreductive surgery [debulking]) for their cancer. 2. 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. 3. 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. 4. Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy). 5. 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. 6. Hemoptysis within four weeks prior to first dose of study drug. 7. Prior major trauma within XX days prior to first dose of study drug. 8. Prior major surgery within XX days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. 9. Prolongation of corrected QT interval (QTc) > 480 msecs. 10. 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 11. 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. 12. Metastatic disease to the brain or leptomeninges.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary objectives for this study are to assess, for each of the dosing regimens described above when combined with daily pazopanib, the following: • Objective response rate, as assessed by CT or MRI scans • CA-125 response rate • 18-week Progression Free Survival (PFS) ;Main Objective: The primary objective of this study is to verify the safety and tolerability of treatment with daily pazopanib (800 mg) added to two regimens of paclitaxel and carboplatin in women with previously untreated, advanced gynaecological tumors: • Paclitaxel 175 mg/m2 and Carboplatin AUC 5 given every 3 weeks for up to 6 cycles (Arm A) • Paclitaxel 175 mg/m2 and Carboplatin AUC 6 given every 3 weeks for up to 6 cycles (Arm B) ;Primary end point(s): • Safety and tolerability of pazopanib in combination with carboplatin and paclitaxel determined by: an assessment of adverse events and changes in laboratory parameters; number of subjects experiencing dose-limiting toxicities; the number, extent, and duration of dose reductions; and the number of subjects discontinuing drug for any reason other than disease progression. | — |
Countries
Belgium, France, Germany
Outcome results
None listed