A Comparison of 2 Standard Doses of Bevacizumab in Combination With Chemotherapy in Epithelial Ovarian Cancer

Inclusion Criteria:

• Histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal,or fallopian tube carcinoma according to WHO Classification of tumours that isadvanced/metastatic/recurrent or unresectable and for which no curative therapyexists.

• Platinum resistant disease (progression within six months of completing aplatinum-containing protocol). In this case, progression from the last line oftherapy would be defined as radiologic progression by RECIST 1.1 criteria on CT orMR.

• Presence of clinically and/or radiologically documented disease. All radiologystudies must be performed within 28 days of randomization.

• All patients must have measurable disease as defined by RECIST 1.1. The criteria fordefining measurable disease are as follows:

• Chest x-ray > 20 mm

• CT scan (with slice thickness of 5 mm) > 10 mm longest diameter

• Physical exam (using calipers) > 10 mm Lymph nodes by CT scan > 15 mm measuredin short axis

• Patients must be >= 18 years of age.

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance statusof 0, 1, or 2.

• Any number of prior lines of treatment is permitted. However, all patients must havereceived at least one prior regimen of chemotherapy including platinum. All patientsmay have received other therapies including immunotherapy, hormone therapy, or PARPinhibitors.

• Patients must have never received an anti-angiogenesis inhibitor includingbevacizumab.

• A BC Cancer "Compassionate Access Program" (CAP) request must be approved prior totreatment

• Radiation: prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of treatmentinitiation. Exceptions may be made for low-dose, non-myelosuppressive radiotherapyafter consultation with sponsor.

• Surgery: Previous surgery is permitted provided that a minimum of 28 days (4 weeks)have elapsed between any major surgery and date of randomization/registration, andthat wound healing has occurred.

• Women of childbearing potential must have agreed to use a highly effectivecontraceptive method during the study and for up to 5 months after the last dose ofchemotherapy/bevacizumab. A woman is considered to be of "childbearing potential" ifshe has had menses at any time in the preceding 12 consecutive months. In additionto routine contraceptive methods, "effective contraception" also includesheterosexual celibacy and surgical sterility defined as a hysterectomy, bilateraloophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner.

• Patient consent must be appropriately obtained in accordance with applicable localand regulatory requirements. Each patient must sign a consent form prior to anystudy specific procedures (see Section 6.0) to document their willingness toparticipate.

Patients who cannot give informed consent (i.e. mentally incompetent patients, or those physically incapacitated such as comatose patients) are not to be recruited into the study. Patients competent but physically unable to sign the consent form may have the document signed by their Legally Acceptable Representative (LAR) or legal guardian. Each patient will be provided with a full explanation of the study before consent is requested.

• Patients must be accessible for treatment and follow-up. Patients registered on thistrial must be treated and followed at the participating centre. This implies theremust be reasonable geographical limits. Investigators must assure themselves thepatients registered on this trial will be available for complete documentation ofthe treatment, response assessment, adverse events, and follow-up.

Exclusion Criteria:

• Patients with a history of other active or current malignancies that require activetreatment.

• Patients with serious illness or medical conditions that might be aggravated bytreatment or limit compliance including, but not limited to:

• History of significant neurologic or psychiatric disorder which would impairthe ability to obtain consent or limit compliance with study requirements.

• Uncontrolled hypertension

• Active uncontrolled or serious infection (viral, bacterial or fungal)

• Other medical conditions that might be aggravated by study treatment

• Patients receiving concurrent treatment with other anti-cancer therapy orinvestigational agents.

• Neutrophils less than 1 x 10^9 /L

• Pregnancy or breastfeeding

• Bleeding diathesis

• History of bowel obstruction or unresolved bowel obstruction (refer to the BC Cancerprotocols above)

• Uncontrolled arterial or venous thromboembolism (note: once controlled, patient maystill be eligible).

• Myocardial infarction (MI) or cerebrovascular accident (CVA) within 4 months.

• Untreated or uncontrolled central nervous system (CNS) metastatic disease.

• Open, non-healing wounds or known fistulas that have not healed.