['metastatic breast cancer']
['paclitaxel', 'azd5363', 'placebo']

        Inclusion Criteria:

          1. Written informed consent prior to admission to this study

          2. Women, age > 18 years

          3. Histologically confirmed breast cancer

          4. Metastatic or locally recurrent disease; locally recurrent disease must not be
             amenable to resection with curative intent (patients who are considered suitable for
             surgical or ablative techniques following potential down-staging with study treatment
             are not eligible)

          5. Patient must have

               -  At least one lesion, not previously irradiated, that can be measured accurately
                  at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have
                  short axis ≥15mm) with CT, or magnetic resonance imaging (MRI) which is suitable
                  for accurate repeated measurements, OR

               -  lytic or mixed bone lesions in the absence of measurable disease as defined
                  above; patients with sclerotic/osteoblastic bone lesions only in the absence of
                  measurable disease are not eligible.

          6. Radiological or clinical evidence of recurrence or progression

          7. Triple-negative disease

          8. Formalin fixed paraffin embedded tumour sample from the primary or recurrent cancer
             must be available for central testing

          9. Patients must be able to swallow and retain oral medication

         10. Haematologic and biochemical indices within protocol specified ranges

         11. ECOG performance status 0-2

         12. Non-childbearing potential. If patient is of childbearing potential, she must have a
             negative serum pregnancy test and agree to use adequate contraception

         13. Willing and able to provide written informed consent

        Exclusion Criteria:

          1. Patients with confirm brain metastases or a history of primary central nervous system
             tumours or who have signs/symptoms attributable to brain metastases and have not been
             assessed with radiologic imaging to rule out the presence of brain metastases.

          2. Prior chemotherapy for metastatic breast cancer

          3. Radiotherapy with a wide field of radiation within 4 weeks before the first dose of
             study medication

          4. Prior treatment with PI3K inhibitors, AKT inhibitors or mTOR inhibitors

          5. Prior treatment with paclitaxel or docetaxel in the (neo)adjuvant setting within 12
             months from inclusion into this study

          6. Pre-existing sensory or motor polyneuropathy ≥ Grade 2 according to CTCAE

          7. Malabsorption syndrome or other condition that would interfere with enteral absorption

          8. Clinically significant pulmonary dysfunction

          9. Prolongation defined as a QTc interval >470msecs or other significant abnormalities in
             rhythm, conduction or morphology of resting ECG including 2nd degree (Type II) or 3rd
             degree AV block or bradycardia (ventricular rate <50 beats/min)

         10. Any factors that increase risk of QTc prolongation or risk of arrythmic events

         11. Experience of any of the following procedures or conditions in the preceding 6 months:
             coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction,
             angina pectoris, congestive heart failure NYHA Grade ≥2, or cardiac ejection fraction
             outside institutional range of normal or <50%

         12. Clinically significant abnormalities of glucose metabolism

         13. Patients with proteinuria or creatine >1.5xULN concurrent with creatinine clearance
             <50mL/min

         14. Exposure to potent inhibitors or inducers or substrates of CYP3A4 or substrates of
             CYP2D6 within 2 weeks before the first dose of study treatment

         15. Concurrent treatment with other experimental drugs or participation in another
             clinical trial with any investigational drug within 30 days prior to study entry

         16. Psychological, familial, sociological or geographical conditions that do not permit
             compliance with the study protocol.

         17. Detained persons or prisoners

         18. Pregnant or nursing women
      