A Phase Ib and Randomised Phase II Trial of Pazopanib With or Without Fosbretabulin in Advanced Recurrent Ovarian Cancer
The first part of this study is to find the recommended dosages of a combination of two drugs: pazopanib and fosbretabulin, which will be given to female patients with relapsed ovarian cancer. The second part of the study involves comparing the recommended dose of pazopanib and fosbretabulin in combination against pazopanib alone in female patients with relapsed ovarian cancer to determine whether the combination is more beneficial that pazopanib on it's own.
• 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.