Bevacizumab and Tocotrienol in Recurrent Ovarian Cancer

Inclusion Criteria:

• Histologically confirmed epithelial ovarian cancer, primary fallopian or primaryperitoneal cancer.

• Platinum resistant epithelial ovarian cancer treated with at least two differentprevious chemotherapeutic regimens

• Progression on previous treatment. Previous treatment with bevacizumab is allowed.

• Measurable disease by the RECIST 1.1 criteria or evaluable by the GCIG CA-125criteria.

• Age ≥ 18 years.

• Performance status 0-2.

• Adequate bone marrow function, liver function, and renal function (within 7 daysprior to inclusion):

• WBC ≥ 3.0 x 10^9/l or neutrophils (ANC) ≥ 1.5 x 10^9/l

• Platelet count ≥ 100 x 10^9/l

• Hemoglobin ≥ 6 mmol/l

• Serum bilirubin < 2.0 x ULN

• Serum transaminase ≤ 2.5 x ULN

• Serum creatinine ≤ 1.5 ULN

• Urine dipstick for protein < 2+. If the dipstick shows protein ≥ 2+, 24 hour urinetesting must be performed and show protein contents < 1 g.

• Written informed consent

Exclusion Criteria:

• Other malignant disease within 3 years prior to inclusion in the study, exceptcuratively treated basal cell or squamous cell carcinoma of the skin.

• Other experimental therapy or participation in another clinical trial within 28 daysprior to treatment initiation.

• Intestinal infiltration or infiltration in major blood vessels at the discretion ofthe treating physician.

• Underlying medical disease not adequately treated (diabetes, cardiac disease).

• Uncontrolled hypertension (BP > 150/100 despite antihypertensive treatment).

• Surgery including open biopsy, within 4 weeks prior to first dose of bevacizumab.

• Cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhagewithin 6 months before start of treatment.

• Clinical significant cardiovascular disease, including:

• Myocardial infarction or unstable angina within 6 months before start oftreatment

• New York Heart Association (NYHA) class ≥ 2

• Poorly controlled cardiac arrhythmia despite medication

• Peripheral vascular disease grade ≥ 3

• Allergy to active substance or any of the auxiliary agents

• Bleeding tumor

• Pregnant or breast-feeding patients. For fertile women a negative pregnancy test atscreening is mandatory.

• Fertile patients not willing to use effective methods of contraception duringtreatment and for 6 months after the end of treatment.