European Trial on Enhanced DNA Repair Inhibition in Ovarian Cancer

Exclusion Criteria

• •Patients who meet any of the following criteria will be excluded from study entry:
• •* Ovarian tumours with low malignant potential (i.e. borderline tumours)
• •* Any prior radiotherapy to the pelvis or abdomen, or any radiotherapy encompassing \> 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 is permitted
• •Second- or third-degree atrioventricular (AV) block, except: treated with a permanent pacemaker Complete left bundle branch block (LBBB)
• •History of evidence of haemorrhagic disorders, patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorders, coagulopathy or tumour involving major vessels.
• •Participation in another clinical study with experimental therapy within 28 days before start of treatment.
• •Participant must not be simultaneously enrolled in any interventional clinical trial.
• •Women who are pregnant or are lactating
• •Patients unable to be regularly followed for any reason (geographic, familiar, social, psychologic, housed in an institution eg. prison because of a court agreement or administrative order)
• •Subjects that are dependent on the sponsor/CRO or investigational site as well as on the investigator.
• •History of known hypersensibility against any medication used in the study
• •Intolerance / Hypersensitivity reactions to components and excipients of study drugs
• •Peripheral neuropathy of grade \>2 per NCI CTCAE, version 4.03, within 4 weeks prior to randomisation
• •Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study