BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients

Inclusion Criteria for Phase I Only:

• Histologically or cytologically proven diagnosis of epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, including all histological subtypes and carcinosarcoma.

Inclusion Criteria for Phase II Only:

• Histologically proven diagnosis of epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer.
• Progression-free interval between 4 to 9 months after first line chemotherapy or 4 to 12 months after second-line chemotherapy with a platinum (cisplatin or carboplatin) based regimen.
• Subjects must have progressed (based on GCIG CA125 and/or RECIST criteria) after last platinum based regimen.
• Subjects must be assessable for response based on GCIG CA125 and/or RECIST criteria.
• Subjects with clinically evident ascites and/or pleural effusions must be assessable by RECIST.
• Study treatment both planned and able to start within 7 days of randomisation

Exclusion Criteria for Phases I and II:

• Non-epithelial ovarian cancer and ovarian tumours of low malignant potential (borderline tumours)
• More than two prior chemotherapy regimens for ovarian cancer (excluding hormonal therapy or biologic agents).
• Any prior chemotherapy for other cancers, but >10 years permitted for phase II only, except for high dose chemotherapy/autologous or allogeneic transplantation
• Chemotherapy within 20 days prior to registration.
• Hormonal therapy or biologic therapy within 28 days prior to registration
• Concurrent treatment with any experimental drugs or other anti-cancer therapy.
• Concurrent treatment with clopidogrel, ticlopidine, persantin and other antiplatelet agents
• Radiotherapy within 21 days prior to registration, or to greater than 15% of the bone marrow.
• Persistent toxic effects of previous chemotherapy of greater than Grade 1 severity (CTCAE v 4, appendix 8)
• Known brain or leptomeningeal disease (baseline CT brain or MRI is only required if there is clinical suspicion of central nervous system involvement).
• Subjects with other invasive malignancies who had (or have) any evidence of another cancer present within the last 3 years, with the exception of early stage non-melanoma skin cancer, carcinoma in situ of cervix, and synchronous endometrial cancer (stage 1 G1,2)
• Untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction (unstable angina, congestive cardiac failure, myocardial infarction) within the previous year, or cardiac ventricular arrhythmias requiring medication, or history of 2nd or 3rd degree atrioventricular conduction defects.
• Cerebrovascular accident or transient ischemic attack within 6 months prior to registration.
• Poorly controlled hypertension: systolic BP >150 or diastolic BP >100 mmHg. Antihypertensive medications are permitted but BP must be ≤150 systolic and ≤100 diastolic on 2 readings separated by at least 24 hours.
• Deep vein thrombosis, pulmonary embolism, within 6 months of registration or arterial thrombosis, or arterial embolism within 12 months prior to registration.
• Receiving full dose, therapeutic anti-coagulation with warfarin, related oral anti-coagulants or unfractionated or low molecular weight heparin. Low dose heparin given for prophylaxis, and aspirin at a dose ≤ 325 mg/day is acceptable.
• Significant infection including active hepatitis B, hepatitis C with abnormal liver function tests, or HIV. Testing for these is not mandatory. Screening for Hepatitis B should be as per institutional policy. Patients known to be Hep B surface antigen positive will be not be eligible even if on antiviral treatment.
• Serious medical or psychiatric conditions which might prevent management according to the protocol.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomisation
• Pregnancy, lactation, or inadequate contraception. Women must be post menopausal or sterile, or use two reliable means of contraception. Women of childbearing potential must have a pregnancy test taken and proven negative within 7 days prior to registration.
• Life expectancy of less than 12 weeks.

Exclusion Criteria for Phase II only:

• Carcinosarcoma and mucinous carcinoma