E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
previously untreated, advanced gynaecological tumors |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014743 |
E.1.2 | Term | Endometrial carcinoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046821 |
E.1.2 | Term | Uterine sarcoma NOS |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016180 |
E.1.2 | Term | Fallopian tube cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052171 |
E.1.2 | Term | Peritoneal carcinoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051963 |
E.1.2 | Term | Vulvar carcinoma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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)
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E.2.2 | Secondary objectives of the trial |
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)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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 cytotoxic chemotherapy. 3. Limited or localized prior radiotherapy is allowed if radiotherapy field did not include extensive bone marrow exposure (e.g., intracavitary radiotherapy is allowed but external beam pelvic radiotherapy is not). 4. Histological confirmation of a malignant gynecologic tumor, e.g., epithelial ovarian cancer, endometrial carcinoma, uterine sarcoma, mixed Müllerian tumour, fallopian tube carcinoma, primary peritoneal carcinoma, cervical carcinoma or vulvar carcinoma. 5. Performance status must be ECOG 0-1. 6. Adequate organ system function as defined in Table 6 of the protocol 7. A female is eligible to enter and participate in this study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: • A hysterectomy • A bilateral oophorectomy (ovariectomy) • A bilateral tubal ligation • Is post-menopausal Patients 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). Patients must discontinue HRT prior to study enrollment due to the potential for inhibition of CYP enzymes that metabolize estrogens and progestins. 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. If a female patient is determined not to be post-menopausal, they must use adequate contraception, as defined immediately below. 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, has used adequate contraception since the pregnancy test and agrees to use adequate contraception as described below. 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 patient’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 patients who are lactating should discontinue nursing prior to the first dose of investigational product and should refrain from nursing throughout the treatment period and for 14 days following the last dose of investigational product. 8. Recovered from the effects of surgery. |
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E.4 | Principal exclusion criteria |
1. Prior radiotherapy that may limit ability to tolerate myelosuppressive chemotherapy, e.g. external beam radiotherapy to the pelvis. Limited or localized prior radiotherapy and prior intracavitary therapy is allowed. 2. Prior use of cytotoxic anticancer therapy. Prior non-cytotoxic anticancer therapy is acceptable if the patient has recovered from all effects of therapy. 3. Presence of bulky, residual, squamous cell tumors. 4. 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. 5. 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. 6. Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy). 7. 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. 8. Hemoptysis within four weeks prior to first dose of study drug. 9. Prior major trauma within 14 days prior to first dose of study drug. 10. Prior major surgery within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. 11. Prolongation of corrected QT interval (QTc) > 480 msecs. 12. 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 • 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. 13. Metastatic disease to the brain or leptomeninges. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability of pazopanib in combination with carboplatin and paclitaxel |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
multicentre, two-arm, feasibility |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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patients will be followed for 28 days after last dose of drug or until adverse events decreased to grade 1 (as outlined in protocol). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |