Nintedanib For HER2-Negative Metastatic Inflammatory Breast Cancer (MIBC)

Exclusion Criteria

• •1. Patients have an active infection and require IV or oral antibiotics.
• •2. Patients have impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) History or presence of serious uncontrolled ventricular arrhythmias or presence of atrial fibrillation; b) Clinically significant resting bradycardia (\< 50 beats per minute); c) LVEF assessed by 2-D echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) \< 45%; d). pericardial effusion
• •3. Any of the following within 6 months prior to study entry: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF) \> NYHA II, Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE),
• •4. Uncontrolled hypertension defined by an SBP\>150 and/or a DBP\>100 mm Hg with or without anti-hypertensive medication
• •5. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug as determined by the investigator.
• •6. Patients have a concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety as determined by the investigator.
• •7. Patients with only locally or regionally confined disease without evidence of metastatic disease
• •8. Prior treatment with BIBF 1120 or any other VEGFR inhibitor within 4 weeks
• •9. Known hypersensitivity to the trial drugs , to their excipients or to contrast media
• •10. Chemotherapy, hormonal therapy, radiotherapy (except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug
• •11. Persistence of toxicity from previous chemo and/or radiotherapy \> grade 2.
• •12. 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).
• •13. Radiographic evidence of cavitary or necrotic tumors
• •14. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
• •15. Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
• •16. 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
• •17. Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
• •18. History of clinically significant haemorrhagic or thromboembolic event in the past 6 months
• •19. Known inherited predisposition to bleeding or thrombosis
• •20. Proteinuria CTCAE grade 2 or greater
• •21. Creatinine \>/= 1.5 x ULN or GFR \< 45 ml/min
• •22. Hepatic function: total bilirubin outside of normal limits; ALT or AST \>1.5 x ULN in pts without liver metastasis. For Pts with liver metastasis: total bilirubin outside of normal limits, ALT or AST \>2.5 x ULN
• •23. Coagulation parameters: International normalised ratio ( INR) \> 2, prothrombin time (PT) and partial thromboplastin time (PTT) \> 50% of deviation of institutional ULN
• •24. Absolute neutrophil count ( ANC) \< 1500/ml, platelets \< 100000/ml, Haemoglobin \< 9.0 g/dl
• •25. Other malignancies within the past 5 years other than basal cell skin cancer or carcinoma in situ of the cervix
• •26. Known history of active or chronic hepatitis C and/or B infection
• •27. Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
• •28. Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females) during the trial and for at least three months after end of active therapy (Contraception in patients with preserved reproductive capacity, patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.)
• •29. Patients with child bearing potential must have a negative pregnancy test (urine or serum) prior to study treatment
• •30. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
• •31. Active alcohol or drug abuse
• •32. Significant weight loss (\> 10% of BW) within past 6 months prior to inclusion into the trial