A Phase II, Open-Label, Multicenter Feasibility Study of Pazopanib, Carboplatin, and Paclitaxel in Women with Previously Untreated, Advanced Gynaecological Tumors

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10051963Term: Vulvar carcinoma; previously untreated, advanced gynaecological tumors; MedDRA version: 9.1Level: LLTClassification code 10033128Term: Ovarian cancer; MedDRA version: 9.1Level: LLTClassification code 10014743Term: Endometrial carcinoma; MedDRA version: 9.1Level: LLTClassification code 10046821Term: Uterine sarcoma NOS; MedDRA version: 9.1Level: LLTClassification code 10016180Term: Fallopian tube cancer; MedDRA version: 9.1Level: LLTClassification code 10052171Term: Peritoneal carcinoma; MedDRA version: 9.1Level: LLTClassification code 10008229Term: Cervical cancer

• Registration Number: EUCTR2007-002918-19-BE
• Lead Sponsor: GlaxoSmithkline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06-26
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 52

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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified