A Clinical Trial in Patients With Breast Cancer Susceptibility Gene (BRCA) Defective Tumours

Inclusion Criteria

• •1. Patients with proven BRCA1 or BRCA2 mutations and after appropriate exposure to standard treatment, as defined by:
• •Breast Cancer
• •* Patients with initially histologically or cytologically proven locally advanced or metastatic breast cancer who may have received up to 3 previous lines of chemotherapy in the locally advanced or metastatic breast cancer setting.
• •* Patients must have previously had a taxane and an anthracycline in either the adjuvant or metastatic setting, provided that these were not contraindicated.
• •* Patients with hormone responsive disease should have had at least 1 line of hormone therapy for metastatic disease.
• •* Prior treatment with a poly-Adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitor is permissible.
• •OR Ovarian Cancer
• •* Patients with initially histologically or cytologically proven ovarian cancer.
• •* Patients must have disease that is platinum resistant or in whom further platinum based therapy is inappropriate.
• •* Prior treatment with a PARP inhibitor is permissible.
• •2. Patients must have measurable disease on computerized tomography (CT) or Magnetic resonance imaging (MRI) scan as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
• •3. Age ≥18 years.
• •4. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
• •5. Life expectancy \>12 weeks.
• •6. Written informed consent.
• •7. Patient willing and able to comply with all protocol requirements.
• •8. No prior anti-cancer treatment in previous 4 weeks, other than palliative radiotherapy (RT).
• •9. Haematological and biochemical indices within the ranges shown below.
• •* Laboratory Test Value required
• •* Haemoglobin (Hb) \> 10g/dL
• •* White Blood Count (WBC) \> 3x109/L
• •* Platelet count \> 100,000/μL
• •* Absolute Neutrophil count \> 1.5x109/L;
• •* Serum bilirubin ≤ 2 x Upper limit normal (ULN)
• •* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) or ALT ≤ 5 x ULN (liver metastasis)
• •* or ≤ 3 x ULN (no liver metastasis)
• •* Alkaline phosphatase ≤ 5 x ULN
• •* Serum creatinine ≤ 1.5 x ULN
• •10. Ascites and pleural effusions must be drained prior to therapy.
• •7. Patients who have received anticancer agent(s) or an investigational agent within 28 days prior to study drug administration.
• •8. Subjects who have not recovered to within one grade level (not to exceed grade 2) of their baseline following a significant adverse event or toxicity attributed to previous anticancer treatment are excluded.