European Trial on Enhanced DNA Repair Inhibition in Ovarian Cancer

Inclusion Criteria

• Patients must meet the following criteria to be eligible for study entry:
• Ability to understand and willingness to sign and date a written informed consent document
• Female patients ≥18 years of age
• High-grade serous, high-grade endometrioid, undifferentiated epithelial ovarian cancer, carcinosarcoma, fallopian tube or primary peritoneal cancer
• Platinum-sensitive relapse >6months after previous platinum-based treatment (calculated from the first day of the last cycle of the last platinum-based chemotherapy until the date of progression confirmed according to RECIST 1.1 on imaging)
• No limits in number of prior lines
• Measurable or evaluable disease according to RECIST 1.1
• ECOG performance status 0-1
• Adequate functions of the bone marrow
• Platelets ≥ 100 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Adequate function of the organs
• Creatinine 1 year
• Patients who have been amenorrhoeic for 20 % of the bone marrow within 2 weeks, or any radiotherapy within 1 week prior to Day 1 of protocol therapy
• Surgery (including open biopsy and traumatic injury) within 4 weeks prior to first dose of Ganetespib, or anticipation of the need for major surgery during study treatment
• Minor surgical procedures, within 24 hours prior to the first study treatment
• Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Any serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.

• Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (>325 mg/day).
• Patients with a history of diagnosis, detection or treatment of any prior malignancies ≤ 2 years prior to initiating protocol therapy, except: basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated.
• Clinically significant gastro-intestinal (GI) tract abnormalities that may increase the risk for GI bleeding and / or perforation including but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding; inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), history of bowel obstruction within 1 year prior to first study treatment (excluding postoperative, i.e. within 4 weeks post surgery), other GI condition with increased risk of perforation such as recurrence deeply infiltrating into the muscularis or mucosa of the rectosigmoid or the mucosa of the bladder, or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
• Non-healing wound or non-healing bone fracture
• Patients with symptomatic brain or leptomeningeal metastases (patients who are asymptomatic since treatment of brain or leptomeningeal metastases, eg. after irradiation, are eligible)
• Left ventricular ejection fraction (LVEF) defined by ECHO below the institutional lower limit of normal
• Cerebrovascular accident (CVA)/ stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤ 6 months prior to first study treatment.
• Significant cardiac disease: New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary atrial or ventricular cardiac arrhythmias
• History of prolonged QT syndrome, or family member with prolonged QT syndrome
• QTc interval > 470 msec when 3 consecutive ECG values are averaged
• Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs i