Trial of Letrozole + Palbociclib/Placebo in Metastatic Endometrial Cancer

Inclusion Criteria: 1. Histological confirmed endometrial cancer of endometrioid type. Mixed tumor histology is allowed if the non-endometrioid component is less than 5%. Tumor must be estrogen receptor positive. 2. Patients may have received adjuvant chemotherapy for stage 1 or 2. 3. Patients may have received any lines of chemotherapy for primary advanced (stage 3-4) or relapsed disease. 4. Patients may have received external beam radiotherapy, brachytherapy, and surgery. 5. Patient may have received maximum one line of endocrine therapy containing MPA/Megace only. 6. Patients must have measureable disease or evaluable disease on CT scan according to RECIST 1.1 outside irradiated field. 7. Patients must give informed consent 8. Patients must have a WHO performance status of 0-1 9. Patients must have an adequate bone-marrow, renal and hepatic function 10. Life expectancy of at least 12 weeks 11. Patients must be fit to receive combination therapy 12. Patient's age \>18 years 13. Patient is post-menopausal. Patients under the age of 55 with intact ovaries shall undergo hormonal verification. 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. Non-endometrioid adenocarcinomas, sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers. 2. Previous anti-cancer endocrine therapy other than MPA/Megace. This means that eg. tamoxifen is not allowed prior to study entry. 3. Concurrent cancer therapy 4. Previous treatment with Palbociclib or other CDK inhibitors. 5. Concurrent treatment with an investigational anticancer agent or participation in another anticancer clinical trial within 21 days before entering into study. 6. Treatment within 21 days prior to randomization with any investigational drug, radiotherapy, 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. 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. 9. Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed. 10. Evidence of significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgment, makes the patient inappropriate for this study. 11. Known uncontrolled hypersensitivity to the investigational drugs. 12. History of major thromboembolic event defined as: 13. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months. 14. History of clinically significant hemorrhage in the past 3 months. 15. Uncontrolled and/or symptomatic CNS metastasis or leptomeningeal carcinomatosis (dexamethasone/prednisone therapy will be allowed if administered as stable dose for at least one month prior randomization). 16. Significant cardiovascular diseases, including uncontrolled hypertension, uncontrolled clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure \> NYHA III, severe peripheral vascular disease, clinically significant pericardial effusion. 17. 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. 18. Active or chronic hepatitis C and/or B infection 19. Persistence of clinically relevant grade 3-4 therapy related toxicity from previous chemo and/or radiotherapy 20. Known hypersensitivity to the trial drugs, or to their excipients. 21. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug 22. Unable or unwilling to swallow tablets/capsules