A Randomized Phase II Study of Paclitaxel/Carboplatin With or Without Sorafenib in the First-Line Treatment of Patients With Stage III/IV Epithelial Ovarian Cancer

Inclusion Criteria:

1. Histologically confirmed, stage III or IV epithelial ovarian carcinoma

2. No previous treatment with chemotherapy or radiation therapy

3. All patients must have undergone cytoreductive surgery, with the following results:

1. No residual tumor nodule > 3cm

2. No residual tumor involvement of the bowel (ie. invasion into bowel wall)

3. No residual intestinal obstruction

4. Measurable or evaluable disease. Patients with elevated CA-125 levels and/or
evaluable disease per RECIST criteria are eligible.

5. ECOG performance status 0 or 1.

6. ANC ≥ 1500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9.0 g/dL.

7. 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)

8. Serum creatinine _ 1.5 x ULN

9. 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.

10. Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to start of treatment.

11. Patients must be able to understand the nature of this study and give written
informed consent.

Exclusion Criteria:

1. Age < 18 years

2. 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

3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

4. Patients with CNS metastases. Patients with neurological symptoms must undergo a CT
scan/MRI of the brain to exclude brain metastasis.

5. Uncontrolled hypertension defined as systolic blood pressure > 150mmHg or diastolic
pressure > 90mmHg, despite optimal medical management

6. Known HIV, chronic hepatitis B or chronic hepatitis C infections

7. 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.

8. Active clinically serious infection (> grade 2)

9. Thrombotic or embolic events such as cerebral vascular accident including transient
ischemic attacks within the last 6 months.

10. Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of starting treatment.

11. Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of starting treatment

12. Serious non-healing wound, ulcer, or bone fracture

13. Evidence of history of bleeding diathesis or coagulopathy

14. Major surgery, open biopsy, or significant traumatic injury within 4 weeks of
starting treatment.

15. Any condition that impairs the ability to swallow whole pills

16. Patients with any type of malabsorption

17. Known or suspected allergy to any of the agents used in this treatment

18. Use of St. John's Wort or rifampin