
    lack of efficacy
  
['advanced gastric adenocarcinoma']
['azd5363', 'paclitaxel', 'azd2014', 'paclitaxel']

        Inclusion Criteria:

          1. Provision of fully informed consent prior to any study specific procedures.

          2. Patients must be ≥20 years of age.

          3. Advanced gastric adenocarcinoma that has progressed during or after first-line
             therapy.

               -  The 1st line regimen must have contained doublet 5-fluoropyrimidine and platinum
                  based regimen.

               -  Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy
                  containing doublet 5-fluoropyrimidine and platinum-based regimen could be
                  considered as first line therapy.

          4. Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months
             prior to starting the first line therapy.

          5. Provision of tumor sample (from either a resection or biopsy)

          6. Patients with biomarker negative

          7. Patients are willing and able to comply with the protocol for the duration of the
             study including undergoing treatment and scheduled visits and examinations.

          8. Eastern Cooperative Oncology Group performance status 0-1.

          9. Patients must have a life expectancy ≥ 3 months from proposed first dose date.

         10. Patients must have acceptable bone marrow, liver and renal function measured within 28
             days prior to administration of study treatment as defined below:

               -  Haemoglobin ≥9.0 g/dL (transfusion allowed)

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               -  White blood cells (WBC) > 3 x 109/L

               -  Platelet count ≥100 x 109/L (transfusion allowed)

               -  Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver
                  metastases are present in which case it must be ≤ 5x ULN

               -  Serum creatinine ≤1.5 x institutional ULN

         11. At least one measurable lesion that can be accurately assessed by imaging or physical
             examination at baseline and following up visits.

         12. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed
             prior to treatment on day 1.

        Exclusion Criteria:

          1. More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy
             with more than 6 month wash out period) for the treatment of gastric cancer in the
             advanced setting.

          2. Any previous treatment with PIK3CA, AKT or mTOR inhibitor or agents with mixed PI3K /
             mTOR activity.

          3. Any previous treatment with paclitaxel

          4. Patients with second primary cancer, except: adequately treated non-melanoma skin
             cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
             curatively treated with no evidence of disease for ≤5 years.

          5. HER2 positive patients

          6. Patients unable to swallow orally administered medication.

          7. Any investigational drug or product administered within 30 days or 5 half-lives,
             whichever is longer, of the first dose of AZD5363.

          8. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative
             reasons), within 3 weeks from the last dose prior to study treatment (or a longer
             period depending on the defined characteristics of the agents used). The patient can
             receive a stable dose of bisphosphonates or denusomab for bone metastases, before and
             during the study as long as these were started at least 4 weeks prior to treatment.

          9. Previous major surgery within 4weeks prior to enrollment.

         10. For AZD2014: Exposure to potent or moderate inhibitors or inducers of CYP3A4/5 if
             taken within the stated washout periods before the first dose of study treatment

         11. With the exception of alopecia, any ongoing toxicities (>Common Toxicity Criteria for
             Adverse Effects grade 1) caused by previous cancer therapy.

         12. Intestinal obstruction or Common Toxicity Criteria for Adverse Effects grade 3 or
             grade 4 upper GI bleeding within 4 weeks before the enrollment.

         13. Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24 hour
             period or family history of long QT syndrome.

         14. Patients with cardiac problem as follows: uncontrolled hypertension (BP ≥150/95 mmHg
             despite medical therapy) Left ventricular ejection fraction <55% measured by
             echocardiography, Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
             , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy,
             Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society
             grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to
             starting treatment

         15. Active or untreated brain metastases or spinal cord compression Patients with treated
             brain metastases or spinal cord compression are eligible if they have minimal
             neurologic symptoms, evidence of stable disease (for at least 1 month) or response on
             follow-up scan, and require no corticosteroid therapy for ≥ 1 week.

         16. Female patients who are breast-feeding or child-bearing

         17. Any evidence of severe or uncontrolled systemic disease, active infection, active
             bleeding diatheses or renal transplant, including any patient known to have hepatitis
             B, hepatitis C or human immunodeficiency virus (HIV)

         18. Patients with proteinuria (3+ on dipstick analysis )
      