Inclusion Criteria:

• Women, 18 years and older, written (signed and dated) informed consent
• Histological confirmed epithelial ovarian cancer, primary cancer of the peritoneum or fallopian tube
• Up to three prior chemotherapies, at least one platinum based chemotherapy
• Platinum refractory or resistant ovarian cancer (defined as stable (SD) or progressive disease (PD) during platinum containing chemotherapy, or treatment free interval < 6 months after stop of platinum based chemotherapy)
• Measurable or non-measurable disease
• Elevated CA°125 level (> 2 x ULN in case of normal CA°125 after prior chemotherapy; or ≥ 2 x nadir CA°125 value after prior chemotherapy, when CA° 125 levels remained elevated above normal) in case of non-measurable disease
• ECOG performance status 0-2
• Negative pregnancy test within 5 days before randomization and adequate contraception in women with childbearing potential

Adequate organ function as defined by the following criteria:

• Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase [SGOT]) and serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase [SGPT]) <=2.5 x upper limit of normal (ULN). If liver function abnormalities are due to underlying malignancy, then AST and ALT may be <=5x ULN
• Total serum bilirubin <=1.5 x ULN
• Prothrombin time (PT) and partial thromboplastin time (PTT) <=1.5 x ULN
• Serum albumin >= 3.0 g/dL
• Absolute neutrophil count (ANC) >=1500/µl
• Platelets >=100,000/µl
• Hemoglobin >=9.0 g/dL
• Serum creatinine <=1.5 x ULN
• TSH within normal range Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures Resolution of all toxic effects of any prior chemotherapy, surgical procedures, radiotherapy, or other cancer related therapies to NCI CTCAE (Version 3.0) grade >=1 and to the baseline laboratory values as defined in inclusion criterion (see before)

Exclusion Criteria:

• Borderline tumor of the ovaries
• Acute or chronic infection
• Any required concurrent cancer chemotherapy or antineoplastic endocrine therapy or radiotherapy
• Exposure to investigational trial medication, cancer chemo- or radiotherapy within the last 28 days prior to start of study treatment
• Known or suspected hypersensitivity to investigational compound
• Second malignancy interfering with prognosis of the patient
• Cachectic patients with a body weight <45 kg
• Patients requiring parenteral nutrition
• Patients with ileus within the last 28 days
• Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event
• Current treatment with therapeutic doses of anticoagulant
• Current treatment with CYP3A4 inhibitors or -inducers
• Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)

• Ongoing cardiac dysrhythmias of NCI CTCAE grade >=2, atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec for females

  • Left ventricular ejection fraction (LVEF) <=50% as measured by echocardiogram
  • NCI CTCAE Grade 3 hemorrhage within 4 weeks of starting study treatment
• Evidence of neurological signs/symptoms suggestive of brain metastases, spinal cord compression, or new evidence of brain or leptomeningeal disease
• Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS)-related illness
• Patients with any other severe concurrent disease, which is an undue risk for the patient by participating in the present study
• Any further condition which according to the investigator results in an undue risk of the patient by participating in the present study
• Major surgery, radiation therapy, or systemic therapy within 3 weeks of first study treatment. At least 7 days should elapse from the time of minor surgical procedure including placement of an access device or fine needle aspiration before randomization into this study can occur.
• Wounds that have not completely healed, active ulcer(s), or bone fracture(s).
• Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
• Prior radiation therapy to >25% of the bone marrow.