Paclitaxel and Carboplatin With Or Without Sorafenib In The First-Line Treatment Of Patients With Ovarian Cancer

All patients must be at least 4 weeks from cytoreductive surgery before starting treatment. Patients will be randomized to receive treatment with either paclitaxel/carboplatin + sorafenib or paclitaxel/carboplatin. Paclitaxel/carboplatin will be repeated every 21 days for a maximum of 6 cycles. Patients with objective response/stable disease after completing 6 courses of chemotherapy will continue sorafenib until disease progression or for a total of 12 months.

• Regimen A:

Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1

Carboplatin AUC 6 infused over 20 minutes IV, Day 1

Sorafenib 400mg PO bid

• Regimen B:

Paclitaxel 175mg/m2, 1-3 hour IV infusion, Day 1

Carboplatin AUC 6.0, 20 minute IV infusion, Day 1

Inclusion criteria

• Histologically confirmed, stage III or IV epithelial ovarian carcinoma
• No previous treatment with chemotherapy or radiation therapy
• All patients must have undergone cytoreductive surgery, with the

following results:

• No residual tumor nodule > 3cm
• No residual tumor involvement of the bowel (ie. invasion into bowel

wall)

• No residual intestinal obstruction
• Measurable or evaluable disease. Patients with elevated CA-125 levels

and/or evaluable disease per RECIST criteria are eligible.

• ECOG performance status 0 or 1.
• ANC ≥ 1500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9.0 g/dL.
• Total bilirubin ≤ 1.5 x upper limits of normal (ULN), ALT and AST ≤ 2.5 x

ULN (≤ 5 x ULN for patients with liver metastases)

• Serum creatinine _ 1.5 x ULN
• INR < 1.5 or a PT/PTT within normal limits. Patients receiving anticoagulation

treatment with an agent such as warfarin or heparin may be

allowed to participate. For patients on warfarin, the INR may be > 1.5,

and should be measured prior to initiation of sorafenib and monitored at

least weekly until INR is stable in the desired therapeutic range.

• Women of childbearing potential must have a negative serum pregnancy

test performed within 7 days prior to start of treatment.

• Patients must be able to understand the nature of this study and give

written informed consent.

Exclusion criteria

• Age < 18 years
• Active cardiac disease, including: A) congestive heart failure > class II

NYHA , B) unstable angina or onset of angina within last 3 months, C) myocardial infarction within 6 months

• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Patients with CNS metastases. Patients with neurological symptoms

must undergo a CT scan/MRI of the brain to exclude brain metastasis.

• Uncontrolled hypertension defined as systolic blood pressure > 150mmHg or diastolic pressure > 90mmHg, despite optimal medical management
• Known HIV, chronic hepatitis B or chronic hepatitis C infections
• Women who are pregnant or lactating. Women of childbearing potential

must agree to use adequate contraception from time of study entry until

at least 3 months after the last administration of study drug.

• Active clinically serious infection (> grade 2)
• Thrombotic or embolic events such as cerebral vascular accident

including transient ischemic attacks within the last 6 months.

• Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of

starting treatment.

• Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of

starting treatment

• Serious non-healing wound, ulcer, or bone fracture
• Evidence of history of bleeding diathesis or coagulopathy
• Major surgery, open biopsy, or significant traumatic injury within 4 weeks

of starting treatment.

• Any condition that impairs the ability to swallow whole pills
• Patients with any type of malabsorption
• Known or suspected allergy to any of the agents used in this treatment
• Use of St. John's Wort or rifampin