Efficacy and Safety of Pazopanib Monotherapy After First Line Chemotherapy in Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• Overall Survival [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
• Safety and tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• 3-year PFS [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• PFS by GCIG criteria [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
• Quality of Life [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]

• Overall Survival [ Designated as safety issue: No ]
• Safety and tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
• 3-year PFS [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• PFS by GCIG criteria [ Designated as safety issue: No ]
• Quality of Life [ Designated as safety issue: No ]

This is a study to determine whether therapy with pazopanib is effective and safe in women with epithelial ovarian, fallopian tube, or primary peritoneal cancer whose cancer has not progressed on first line chemotherapy.

This is a randomized, two-arm, placebo controlled, double-blind, multicenter, intergroup Phase III study in women with non-bulky FIGO Stage II - IV ovarian, fallopian tube, or primary peritoneal cancer that has not progressed (i.e., CR, PR, SD) after completing their first-line chemotherapy for advanced ovarian cancer. Approximately 900 subjects will be enrolled into the study.

• Primary Peritoneal Carcinoma
• Ovarian Cancer
• Neoplasms, Ovarian
• Fallopian Tube Cancer

• Drug: Pazopanib
  Pazopanib 800 mg daily for 104 weeks (24 months)
• Drug: Placebo
  Matching placebo 800 mg daily, for 104 weeks (24 months).

• Experimental: Arm A
  Intervention: Drug: Pazopanib
• Placebo Comparator: Arm B
  Intervention: Drug: Placebo

Inclusion Criteria:

• written informed consent
• At least 18 years old.
• 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.
• Study randomization 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.
• No evidence of disease progression
• ECOG status of 0 or 1.
• Able to swallow and retain oral medication.
• Adequate hematologic, hepatic, and renal system function as follows:

Hematologic

• Absolute neutrophil count (ANC) at least 1.5 X 10^9/L
• Hemoglobin at least 9 g/dL (or 5.59 mmol/L)
• Platelets at least 100 X 10^9/L
• Prothrombin time (PT) or international normalized ratio (INR) up to 1.2 X ULN
• Activated partial thromboplastin time (aPTT) up to 1.2 X ULN Hepatic
• Total bilirubin up to 1.5 X ULN
• AST and ALT up to 2.5 X ULN Renal
• Serum creatinine up to 1.5 mg/dL

Or, if greater than 1.5 mg/dL:

Calculated creatinine clearance at least 50 mL/min Urine Protein

• Urine protein is 0, trace, or +1 determined by dipstick urinalysis, or < 1.0 gram determined by 24- hour urine protein analysis.
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception.

Exclusion Criteria:

• Either (a) bulky disease, or (b) any residual disease which in the opinion of the investigator will need imminent second-line therapy
• Synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless certain conditions are met.
• Clinically significant gastrointestinal abnormalities
• Prolongation of corrected QT interval (QTc) > 480 msecs
• History of any one or more cardiovascular conditions within the past 6 months prior to randomization
• Poorly controlled hypertension
• History of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months prior to randomization
• Major surgery (including interval debulking) or trauma within 28 days, or minor surgical procedures within 7 days, prior to randomization, or has any non-healing wound, fracture, or ulcer.
• Evidence of active bleeding or bleeding diathesis.
• Hemoptysis within 6 weeks prior to randomization.
• Endobronchial metastases.
• 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.
• Investigational or anti-VEGF anticancer therapy prior to study randomization.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.