Inclusion Criteria

INCLUSION CRITERIA

1. All stages of the study (IV and oral):

Patients must be proven known carriers of a mutation of BRCA1 or BRCA2 or considered
to be highly likely to be carriers of a BRCA1 or 2 mutation* (score of ≥ 20 as per
Manchester criteria) and have histologically documented locally advanced or
metastatic breast cancer or advanced ovarian cancer.

*Patients considered highly likely to be carriers will be tested after consenting and
a BRCA1 or 2 mutation must be confirmed for the patient to be eligible to receive
treatment.

Oral stage 1 only:

In addition to the above, patients with high grade serous ovarian cancer with unknown
BRCA status may be entered into oral stage 1.

2. Patients with ovarian cancer (including epithelial, fallopian tube cancer and primary
peritoneal cancer) who have had no more than 5 prior chemotherapy regimens in the
last 5 years. For the BRCA carriers > 2 months must have elapsed since their last
treatment with a carboplatin- or cisplatin-containing regimen or for high grade
serous ovarian cancer patients ≥ 6 months.

3. Patients with breast cancer who have had no more than 5 prior chemotherapy regimens
in the last 5 years.

4. Measurable disease as measured by X-ray, computerised tomography (CT), or MRI scan as
defined by RECIST criteria. These measurements must be done within 4 weeks of the
patient going on study. Clinical measurements must be done within one week of the
patient going on study. Patients with bone disease must have other measurable
disease for evaluation. Previously irradiated lesions cannot be used for measurable
disease.

5. Life expectancy of at least 12 weeks

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

7. Haematological and biochemical indices within the ranges shown below. These
measurements must be performed within one week before the patient goes on study.

Lab Test Value Required Haemoglobin (Hb)
≥9.0 g/dl Neutrophils ≥1.5 x 10^9/L Platelets
(Plts) ≥100 x 10^9/L Serum bilirubin
≤1.5 x upper normal limit Alanine amino-transferase (ALT) and/or ≤ 2.5 x upper
limit of normal (ULN) aspartate amino-transferase (AST) unless due to tumour
in which case up to 5 x ULN is permissible Glomerular Filtration Rate (GFR)
calculated either by the Wright formula ≥50 ml/min or Cockcroft-Gault formula or by
isotope clearance measurement

8. 18 years or over

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

EXCLUSION CRITERIA

1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy,
chemotherapy, biological agents or investigational agents during the previous 4 weeks
(6 weeks for nitrosoureas and Mitomycin-C) before treatment.

2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia
or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug
Development Office (DDO) should not exclude the patient.

3. Known brain metastases.

4. Female patients able to become pregnant (or already pregnant or lactating). However,
those female patients 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 intrauterine device
and condom, diaphragm with spermicidal gel and condom, or are surgically sterilised)
4 weeks before entering the trial, during the trial and for 6 months afterwards are
considered eligible.

5. Male patients with partners of child-bearing potential (unless they agree to use one
form of highly effective contraception such as a barrier method of condom plus
spermicide during the trial and for 6 months afterwards).

6. Major thoracic and/or abdominal surgery in the preceding 4 weeks from which the
patient has not recovered.

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

8. Concurrent malignancies at other sites, 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 concurrent breast and ovarian carcinoma. Cancer survivors,
who have undergone potentially curative therapy for a prior malignancy, are eligible
for the study.

9. Patients with active or unstable cardiac disease or history of myocardial infarction
within 6 months. Patients with cardiovascular signs or symptoms should have a MUGA
scan or echocardiogram, and those patients with left ventricular ejection fraction
(LVEF) below the institutional limit of normal should be excluded.

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

11. Patients who have already received a PARP inhibitor.