
    safety
  
['ovarian neoplasms', 'neoplasms, ovarian', 'ovarian cancer']
['pazopanib', 'fosbretabulin']

        Inclusion Criteria:

          -  Advanced, progressive, recurrent epithelial ovarian, fallopian tube or primary
             peritoneal carcinoma, which has recurred following at least one platinum-containing
             regimen.

          -  Progressive disease according to RECIST 1.1 or GCIG criteria within 3-12 months of
             completing platinum containing therapy, although this need not be the immediately
             preceding regimen.

          -  World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1).

          -  Measurable disease (RECIST 1.1 (Appendix 2) or Progressive Disease (PD) according to
             CA125 GCIG criteria with non-measurable disease on CT scan.

          -  Life expectancy of at least 12 weeks.

          -  Haematological and biochemical indices within the ranges shown below. These
             measurements must be performed within one week (Day -7 to Day 1) before the patient
             receives the first dose of Investigational Medicinal Product (IMP):

               -  Haemoglobin (Hb) ≥ 90 g/L

               -  Absolute neutrophil count ≥ 1.5 x 109/L

               -  Platelet count ≥ 100 x 109/L

               -  Serum potassium within normal range

               -  Bilirubin ≤ 1.5 x upper limit of normal (ULN)

               -  Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 2.5 x ULN
                  unless raised due to hepatic metastatic disease in which case up to 5 x ULN is
                  permissible

               -  Either: Calculated creatinine clearance ≥ 40 mL/min (uncorrected value) Or:
                  Isotope clearance measurement ≥ 40 mL/min (corrected)

               -  Activated partial thromboplastin time (aPTT) ≤ 1.2 x ULN

               -  Prothrombin Time (PT) or International normalised ratio (INR) ≤ 1.3 x ULN

               -  Urine protein dipstick of less than or equal to 2+, or if 2+ or greater the
                  patient must have a 24 hour urinary protein value of less than 2 g.

               -  Clinically euthyroid.

               -  Aged 18 years or over at the time of consent.

               -  Written (signed and dated) informed consent and capable of co-operating with
                  treatment and follow-up.

               -  Patients can have received bevacizumab prior to trial entry providing that the
                  last dose was administered at least 6 months before the first dose of IMP.

        Exclusion Criteria:

          -  Radiotherapy, surgery or tumour embolisation within 28 days before the first dose of
             IMP

          -  Endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six
             weeks for nitrosoureas, Mitomycin-C and six weeks for investigational medicinal
             products) before the first dose of IMP.

          -  Ongoing grade ≥ 2 toxic manifestations of previous treatments. Exceptions to this are
             alopecia or certain Grade 1 toxicities, which in the opinion of the Chief and
             Principal Investigators should not exclude the patient; and grade 1 or 2 neurotoxicity
             considered to be due to paclitaxel.

          -  Female patients who are able to become pregnant (or are already pregnant or
             lactating). Those who have a negative serum or urine pregnancy test before enrolment
             and agree to use two highly effective forms of contraception (oral, injected or
             implanted hormonal contraception and condom, have an intra-uterine device and condom,
             diaphragm with spermicidal gel and condom) for four weeks before entering the trial,
             during the trial and for six months afterwards are considered eligible.

          -  Major thoracic or abdominal surgery from which the patient has not yet recovered.

          -  At high medical risk because of non-malignant systemic disease including active
             uncontrolled infection.

          -  Known to be serologically positive for hepatitis B, hepatitis C or human
             immunodeficiency virus (HIV).

          -  History of any of the following cardiovascular conditions within the last six months:

               -  Coronary revascularisation (percutaneous coronary intervention (PCI) or coronary
                  artery bypass graft (CABG))

               -  Acute coronary syndrome (myocardial infarction (MI), unstable angina)

               -  Symptomatic peripheral vascular disease

               -  Class III or IV congestive heart failure, as defined by the New York Heart
                  Association (NYHA) (Appendix 4)

          -  Patients who have sustained hypertension, defined as a systolic blood pressure (SBP)
             of > 140 mm Hg or diastolic blood pressure (DBP) of > 90 mm Hg, on three occasions.

          -  ECG with evidence of clinically significant abnormalities.

          -  Patients with a QTc> 480ms or taking any drug known to prolong the QTc interval that
             cannot be stopped for the duration of the trial (Appendix 4).

          -  Patients with pathologic bradycardia (<60 b/m in non-athletes), heart block (excluding
             first-degree block, being PR interval prolongation only).

          -  History of cerebrovascular accident (including transient ischaemic attack (TIA)),
             pulmonary embolism or untreated deep vein thrombosis (DVT) within the past six months.
             Patients with recent DVT or pulmonary embolism who have been treated with therapeutic
             anti-coagulant agents for at least six weeks will be eligible, provided their INR (if
             taking oral anti-coagulants) has been stable for this period of time.

          -  History or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis, except for individuals who have previously treated CNS
             metastases, are asymptomatic and have had no requirement for steroids or
             anti-convulsant medication for six months prior to the first dose of IMP.

          -  Clinically significant abnormalities that may increase the risk of gastrointestinal
             bleeding or perforation, including but not limited to:

               -  Bleeding: Active peptic ulcer disease, known intraluminal metastatic lesions with
                  risk of bleeding, Inflammatory bowel disease (Crohn's disease, ulcerative
                  colitis);

               -  Perforation: History of abdominal fistula or large pelvic mass; gastrointestinal
                  perforation or intra-abdominal abscess within four weeks prior to first dose of
                  IMP; previous bowel surgery which is judged by the investigator to increase
                  significantly the risk of gastrointestinal complications from trial treatment

          -  Evidence of active bleeding or bleeding diathesis.

          -  Transfusion within one week prior to first dose of IMP.

          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.

          -  Clinically significant haemoptysis, within eight weeks before the first dose of IMP.

          -  Previous treatment with pazopanib.

          -  Any participant that is participating in (or plans to participate in) another
             interventional clinical trial, whilst taking part in this Phase Ib/II study of
             fosbretabulin and pazopanib. Participation in an observational trial would be
             acceptable.

          -  Any other condition which in the Investigator's opinion would not make the patient a
             good candidate for the clinical trial.

          -  Current malignancies of other types, with the exception of adequately treated
             cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell
             carcinoma of the skin and no evidence of recurrence of other malignancy for at least 2
             years.

          -  Hypersensitivity to Pazopanib or any of it's excipients
      