A Study Comparing AZD2014 vs Everolimus in Patients With Metastatic Renal Cancer

Inclusion Criteria: 1. Histopathologically confirmed renal cell carcinoma with measurable metastases on CT/MRI imaging. Only a component of clear cell is required. 2. Radiological progressive disease on VEGF targeted therapy (RECIST v1.1). Exposure to more than one line of VEGF targeted therapy is acceptable. Previous treatment with initial interferon or IL-2 or other experimental agent is acceptable (with the exception of drugs specifically targeting mTOR). 3. Evidence of measurable disease (ie, ≥1 malignant tumour mass that can be accurately measured in at least 1 dimension ≥ 20 mm with conventional computerized tomography \[CT\] scan or Magnetic Resonance Imaging \[MRI\], or ≥10 mm (except lymph nodes which must have short axis ≥ 15 mm) with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable. 4. Adequate organ function as defined by the following criteria: 1. Total serum bilirubin ≤1.5 x ULN (patients with Gilbert's disease exempt), 2. Serum transaminases ≤3.0 x ULN (x5 in the presence of liver metastasis). 3. Serum creatinine ≤ 2 x ULN or Cockcroft and Gault \>30ml/min 4. Absolute neutrophil count (ANC) ≥1.5 x 109/L without growth factor support, 5. Platelets ≥ 100 x 109/L 5. Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment. 6. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures 7. ECOG performance status of 0, 1 or 2. 8. Life expectance \>12 weeks 9. At least 14 days since the end of prior systemic treatment (sunitinib, pazopanib, sorafenib), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤1 or back to baseline except for alopecia or hypothyroidism. A 21 day gap between bevacizumab and interferon therapy should exist. 10. Fasting blood sugar ≤8mmol/l and HbA1C ≤7% 11. Age ≥18 years Exclusion Criteria: 1. Previous exposure to mTOR inhibitors for metastatic renal cancer. 2. Females of child-bearing potential. The definition of child-bearing potential: women between menarche and menopause who have not been permanently or surgically sterilised and capable of procreation. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception. 3. Pregnant and Breast feeding women. 4. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormally that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgement of the investigator, would make the patient inappropriate for entry into this study. Specifically the following indications are contraindicated: Hereditary galacto-intolerance, glucose/galactose malabsorption and lactose deficiency 5. Untreated clinically symptomatic brain or meningeal metastases. Patients with evidence of clinically stable brain metastases are eligible providing that they do not require corticosteroids. 6. Any evidence of severe or uncontrolled diseases e.g., unstable or uncompensated respiratory, hepatic or renal disease. 7. Evidence of interstitial fibrotic lung disease (bilateral, diffuse, parenchymal lung disease). 8. Unresolved toxicity ≥ CTCAE v.4.0 grade 2 (except alopecia and hypothyroidism) from previous anti-cancer therapy. 9. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ or localised controlled prostate cancer) within 5 years, unless the patient has been disease free for 2 years and there is a tissue diagnosis of the primary cancer of interest from a target lesion. 10. Uncontrolled diabetes mellitus or hyperlipidaemia (\> grade 1) 11. Treatment with an investigational drug (not including VEGF TKIs such as pazopanib/ tivozanib) within 21 days prior to the first dose of therapy. If investigational drug is a VEGF TKI then with 14 days prior to the first dose of therapy 12. Patients who have experienced any of the following procedures or conditions currently or in the preceding 12 months: 1. Coronary artery bypass graft 2. Angioplasty 3. Vascular stent 4. Myocardial infarction 5. Angina pectoris 6. Congestive heart failure new york heart association grade ≥2 7. Ventricular arrhythmias requiring continuous therapy 8. Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled 9. Haemorrhagic or thrombotic stroke, including transient ischaemic attacks or 10. Any other central nervous system bleeding 13. Mean resting QTcF ≥470 msec as per local reading 14. Abnormal ECHO at baseline (left ventricular ejection fraction \[LVEF\] \<50% 15. Known inherited or acquired immunodeficiency 16. Known active hepatitis B or C infection or Known HIV. 17. Other concomitant anti-cancer therapy (including LHRH agonists) except steroids 18. Previous bone marrow transplant 19. Age \<18 years 20. Any haemopoietic growth factors (eg, G-CSF, GM-CSF) within 2 weeks prior to receiving study drug