Combination Chemotherapy With Nintedanib / Placebo in Endometrial Cancer

Inclusion Criteria: 1. Histological confirmed endometrial cancer. (FIGO 2009) 1. Stage 3C 2 2. Stage 4 A \& B 3. Relapsed after adjuvant therapy for stage 1-3 disease 2. Patients may have undergone primary surgery. 3. Patients may have received adjuvant chemotherapy for stage 1 - 3. 4. Patients may have received vaginal brachytherapy 5. Patients may have received external beam radiotherapy. Patients who are to be enrolled for stage 3C2 diseases are allowed to receive external beam radiotherapy prior to trial entry. 6. Patients may have received hormonal treatment 7. Patients must have measurable disease or non-measurable disease on CT scan according to RECIST 1.1 outside irradiated field. For stage 3C2 disease patients without measureable or non-measureable disease are accepted. 8. Patients must give informed consent 9. ECOG performance status of 0 -1 10. Patients must have an adequate organ function 11. Life expectancy of at least 12 weeks 12. Patients must be fit to receive combination chemotherapy 13. Patient's age \>18 years 14. Patients with preserved reproductive capacity must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment Exclusion Criteria: 1. Sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers. 2. Concurrent cancer therapy 3. Previous Chemotherapy for stage 4 disease or for relapsed disease. 4. Previous treatment with anti-angiogenic/anti VEGF therapy including nintedanib. 5. Concurrent treatment with an investigational agent or participation in another clinical trial. 6. Treatment within 28 days prior to randomisation with any investigational drug, radiotherapy, immunotherapy, chemotherapy, hormonal therapy or biological therapy. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases in extremities, provided that the radiotherapy does not involve target lesions, and the reason for the radiotherapy does not reflect progressive disease. 7. Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period. 8. Relapse within six months after adjuvant chemotherapy (treatment-free interval \< 182 days). 9. Previous malignant disease, except patients with other malignant disease, for which the patient has been disease-free for at least three years. Concurrent other malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin. 10. Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed. 11. Evidence of significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgement, make the patient inappropriate for this study. 12. Known contraindications to VEGF directed therapy Target Disease Exceptions 13. Known uncontrolled hypersensitivity to the investigational drugs. 14. History of major thromboembolic event defined as: * Uncontrolled pulmonary embolism (PE) * Deep venous thrombosis (DVT) * Other related conditions, though patients with stable therapeutic anticoagulation for more than three months prior randomization are eligible for this study. 15. History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 3 months. 16. History of clinically significant haemorrhage in the past 3 months. 17. Radiotherapy to the target lesion within the past 3 months prior to baseline imaging 18. Persistant grade 3 or 4 toxicity from previous chemotherapy and/or radiotherapy, except alopecia. Patients with ongoing ≥ Grade 2 neuropathy are to be excluded. 19. Active brain metastases (e.g. stable for \<4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomisation). 20. Leptomeningeal disease 21. Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure \> NYHA II, serious cardiac arrhythmia, pericardial effusion) See Appendix 12. 22. Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwards. 23. Radiographic evidence of cavitating or necrotic tumours with invasion of adjacent major blood vessels. 24. Active or chronic hepatitis C and/or B infection 25. Known hypersensitivity to the trial drugs, or to their excipients. 26. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug 27. Unable or unwilling to swallow tablets/capsules