A Phase III Study to Evaluate the Efficacy and Safety of Pazopanib Monotherapy Versus Placebo in Women Who Have not Progressed after First Line Chemotherapy for Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

Phase 1

• Conditions: Advanced Ovarian Cancer (FIGO Stage II, Stage III, and Stage IV epithelial ovarian, fallopian tube, or primary peritoneal cancer).; MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-004672-50-DK
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-15
• Last Update Posted: 6 November 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 900

Inclusion Criteria

A subject will be considered eligible for inclusion in this study if all the following criteria are met:
1. Subject has provided written informed consent prior to performance of study-specific procedures or assessments, and is willing to comply with treatment and follow-up. Note: Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes
provided these procedures meet the protocol requirements.
2. Subject is >= 18 years old.
3. Subject has histologically confirmed, FIGO stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma that was treated with surgical debulking and at least five cycles of platinum-taxane doublet chemotherapy. Note: Intravenous, intraperitoneal, or neoadjuvant platinum-taxane doublet chemotherapy are
allowed; for weekly therapy, three weeks are considered one cycle. Interval debulking is allowed; second look is also allowed, as long as neither procedure is related to, or indicate, disease progression.
4. The date of study randomization must be at least 3 weeks and not more than 12 weeks from the date of the last chemotherapy dose, and all major toxicities from the previous chemotherapy must have resolved to grade 1 or better.
5. Subject has had no evidence of disease progression throughout their first-line treatment and prior to study randomization, including -CT or MRI scan taken within 6 weeks prior to randomization showing no radiological progression, and -CA-125 measurement taken within 6 weeks prior to randomization showing no CA-125 progression (according to the GCIG criteria, Appendix 2), and - no other clinical evidence of disease progression.
6. Subject has ECOG status of 0 - 2.
7. Subject is able to swallow and retain oral medication.
8. Subject has adequate hematologic, hepatic, and renal system function as defined in the protocol.
9. Subject 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.
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 HRT and whose menopausal status is in doubt will be required to use a highly effective
method of contraception (outlined below) if they wish to continue with 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. If a female subject is
determined not to be post-menopausal, they must use adequate contraception, as defined immediately below.
OR
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 th

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1. Subject has either (a) bulky disease (eg, ascites that causes abdominal distention or requires paracentesis; mesenteric thickening; or tumor masses of 2 cm or more by CT or MRI identified on the baseline scan), or (b) any residual disease which in the opinion of the investigator will need imminent second-line therapy
2. Subjects with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless ALL of the following criteria for describing the endometrial carcinoma are met
- FIGO Stage <= IB, and
- No lymphovascular invasion, and
- Not poorly differentiated (i.e. not Grade 3 or papillary serous or clear cell)
3. Subject has clinically significant gastrointestinal abnormalities including, but not limited to:
- Malabsorption syndrome
- Major resection of the stomach or small bowel that could affect the absorption of study drug (eg, short bowel syndrome)
- Active peptic ulcer disease
- Known intraluminal metastatic lesion/s with suspected bleeding
- Inflammatory bowel disease
- Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess.
4. Subject has prolongation of corrected QT interval (QTc) > 480 msecs in the Screening ECG.
5. Subject has a history of any one or more of the following cardiovascular conditions within the past 6 months prior to randomization:
- 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)
6. Subject has poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140mmHg or diastolic blood pressure (DBP) of >= 90mmHg].
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. At Screening, blood pressure must be assessed on at least two occasions that are separated by a minimum of 24 hours. The mean SBP / DBP values from each blood pressure assessment must be <140/90mmHg in order for a subject to be eligible for the study.
7. Subject has a history of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months prior to randomization.
Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible.
8. Subject has had major surgery (including interval debulking) or trauma within 28 days, or minor surgical procedures (eg, central venous access line removal) within 7 days, prior to randomization, or has any non-healing wound, fracture, or ulcer.
9. Subject has evidence of active bleeding or bleeding diathesis.
10. Subject has had hemoptysis within 6 weeks prior to randomization.
11. Subject has known endobronchial metastases.
12. Subject has any serious and/or unstable pre-existing medical (e.g., uncontrolled infection), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
13. Subject has been administered an investigational or anti-VEGF anticancer therapy prior to study randomization. Schedule, route, and dose variations of registered drugs do not account for investigational drug

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine whether pazopanib (52 weeks of pazopanib 800 mg daily) prolongs progression free survival (PFS)<br>in women with non-bulky, FIGO Stage II-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer that<br>has not progressed after first line chemotherapy.;Secondary Objective: To compare the effect of 52 weeks of pazopanib 800 mg daily versus placebo on<br>- Overall survival (key secondary endpoint)<br>- Safety<br>- PFS by GCIG criteria<br>- 3-year PFS rate<br>- Quality of life (measured using EORTC QLQ-C30 with the OV-28 module, and<br>EuroQOL EQ-5D).;Primary end point(s): The primary endpoint for this study is PFS, defined as the interval between the date of<br>randomization and the date of radiological disease progression (by RECIST criteria) or death due to any cause.