Nintedanib(BIBF1120) in Thyroid Cancer

Inclusion Criteria: * Histologically confirmed differentiated or medullary thyroid cancer by local pathologist. * Available tumor tissue at the time of initial diagnosis for histology review. The provision of tumor tissue for histology review is mandatory for every patient/site. * Locally advanced or metastatic disease deemed incurable by surgery, radiotherapy and/or radioactive iodine (RAI). * No current symptomatic brain metastases or if previously present, must have been treated at least two months before randomization. CT or MRI scan of the brain is mandatory (within 4 weeks prior to randomization) to assess the presence or not of brain metastases. * Patients must have measurable lesion with documented progression during the 12 months prior to randomization, according to RECIST V.1.1. Patients who were withdrawn from first line treatment due to toxicity without documented disease progression or who received placebo (in the context of a clinical trial) as prior treatment are not eligible. * Patients must have received one or 2 prior line of treatment (but no more than two) and must be off treatment for at least 4 weeks prior to randomization. * Age ≥18 years. * Performance status (PS) 0-1 (WHO, Appendix C). * Life expectancy of more than 12 weeks. * No history of other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin. * No ongoing treatment related toxicity due to prior treatment \> grade I (except alopecia). * Adequate organ function, evidenced by the following laboratory results within 3 weeks prior to randomization: (patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry \[with the EXCEPTION of Glomerular Filtration Rate\] are acceptable) * Absolute neutrophil count \> 1500 cells/mm3 * Platelet count \> 100,000 cells/mm3 * Hemoglobin \> 8.5 g/dL * Total bilirubin within normal limits * SGOT (AST), SGPT (ALT), and alkaline phosphatase ≤ 1.5× ULN (or ≤ 2.5× ULN) in the case of presence of liver metastases) * Glomerular Filtration Rate (GFR) ≥ 45 ml/min according to Cockcroft and Gault Formula (see Appendix E.). * Proteinuria CTC-AE \< 2 * Coagulation parameters: International normalized ratio (INR) ≤ 2, prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5x institutional ULN * No history of significant cardiac disease defined as: * Symptomatic CHF (NYHA classes III-IV, see Appendix D) * High-risk uncontrolled arrhythmias, i.e. atrial tachycardia with a heart rate \> 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block (second degree AV-block Type 2 \[Mobitz 2\] or third degree AV-block) * No prolongation of corrected QT interval (QTc) \> 480 msecs, * History of myocardial infarction within 12 months prior to randomization * Clinically significant valvular heart disease * No angina pectoris requiring anti-angina treatment * No current uncontrolled hypertension (persistent systolic \> 180 mmHg and/or diastolic \> 100 mmHg) (with or without medication). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. * No evidence of active bleeding or bleeding diathesis. * No cerebrovascular accident at any time in the past, transient ischemic attack, deep venous thrombosis (DVT) or pulmonary embolism in the past 6 months. * Therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid \< 325mg per day) is not allowed. * No history of clinically significant gastrointestinal disorders including: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation. No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment. * No current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C virus) or any other systemic disease/symptoms that may hamper compliance to study protocol, according to physician's judgment. * No major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment and/or presence of any non-healing wound, fracture, or ulcer. * No history of receiving any investigational treatment within 28 days prior to randomization. * Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. * Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. * Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment. * Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. * Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. * Tissue availability for central confirmation of the histological diagnosis is mandatory. All other TR projects are optional for the patient and a separate consent form for these will be provided to the patient.