Bevacizumab and Trabectedin +/- Carboplatin in Advanced Ovarian Cancer

Inclusion Criteria:

* Age≥18years
* Eastern Cooperative Oncology Group (ECOG)- performance status 0-2
* Cytological/histological diagnosis of epithelial ovarian cancer
* Progression free interval between 6-12 months (calculated from the first day of the last cycle of the previous last platinum-based chemotherapy until the date of progression confirmation through radiologic imaging)
* One or two previous platinum-based chemotherapy lines
* Measurable disease according to RECIST version 1.1
* Life expectancy ≥ 12 weeks
* Patients must be able to receive dexamethasone or its equivalent, as a premedication for trabectedin
* Written informed consents given before the enrolment according to International Conference on Harmonization/ Good Clinical Practice (ICH/GCP).

Exclusion Criteria:

* Prior treatment with trabectedin
* Prior progression while on therapy containing bevacizumab or other vascular endothelial growth factor (VEGF) pathway-target therapy
* Pre-existing grade \> 1 sensitive/motor neurologic disorder
* Current or recent (within 30 days of first study dosing) treatment with another investigational drug
* Surgery (including open biopsy) within 4 weeks prior to the first planned dose of bevacizumab
* Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulant or thrombolytic agent for therapeutic purposes (except for line patency, in which case international normalized ratio (INR) must be maintained below 1.5). Post operative prophylaxis with low molecular weight heparin sc is allowed
* Inadequate bone marrow function: absolute neutrophil count (ANC): \<1.5 x 109/l, or platelet count \<100 x 109/l or haemoglobin \<9 g/dl. Patients may be transfused to maintain haemoglobin values ≥9 g/dl
* Inadequate coagulation parameters: activated partial thromboplastin time (APTT) \>1.5 x upper limit of normal (ULN) or INR \>1.5
* Inadequate liver function, defined as: serum (total) bilirubin \> ULN for the institution AST/serum glutamic-oxaloacetic transaminase (SGOT) or ALT/ serum glutamic-pyruvic transaminase (SGPT) \>2.5 x ULN
* Inadequate renal function: serum creatinine \>1.5 mg/dL or \>132 micromol/L and urine dipstick for proteinuria \> or = 2+ and \>1g of protein in their 24-hour urine collection
* History or evidence of brain metastases or spinal cord compression
* Pregnant, breastfeeding women and women of child bearing potential, who do not agree to use a medically acceptable method of contraception through the treatment period and for 6 months after discontinuation of treatment
* History or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident, stroke or transient ischemic attack or sub-arachnoid haemorrhage within 6 months prior to the first study treatment
* Uncontrolled hypertension (sustained systolic \>150 mmHg and/or diastolic \>100 mmHg despite antihypertensive therapy) or clinically significant (i.e. active) cardiovascular disease, including: myocardial infarction or unstable angina within 6 months prior to the first study treatment, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
* History of bowel obstruction, including subocclusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
* Non-healing wound, ulcer or bone fracture
* hepatitis C virus (HCV) positivity
* Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.