Nintedanib For HER2-Negative Metastatic Inflammatory Breast Cancer (MIBC)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Inflammatory Breast Neoplasms
Intervention: BIBF 1120; Phone Call
Intervention description: Initial dose is 200 mg twice daily orally for a 28 day cycle.; Participant called by a member of the study staff every 3 months for up to 1 year after end-of-treatment visit. These calls should last about 2 minutes.
Intervention MeSH terms: Nintedanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Metastatic inflammatory breast cancer; MIBC; HER2-negative; Breast carcinoma; BIBF 1120; Nintedanib; Phone call

Summary:

      The goal of this clinical research study is to learn if Ofev® (nintedanib, also called
      BIBF1120) can help to control IBC. The safety of this drug will also be studied.

      This is an investigational study. Nintedanib is commercially available and FDA approved for
      the treatment of certain types of lung disease. Its use in this study is investigational. The
      study doctor can explain how the study drug is designed to work.

      Up to 44 participants will be enrolled in this study. All will take part at MD Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients are 18 years of age or older

          2. Patients are female or male.

          3. Have histological confirmation of breast carcinoma with a clinical diagnosis of IBC
             based on presence of inflammatory changes in the involved breast, including diffuse
             erythema and edema (peau d'orange), with or without an underlying palpable mass
             involving the majority of the skin of the breast. Pathological evidence of dermal
             lymphatic invasion should be noted but is not required at diagnosis.

          4. Have confirmed distant metastasis with or without local recurrence.

          5. Have negative HER2 expression by IHC (defined as 0 or1+), or FISH. If HER2 is 2+,
             negative HER2 expression must be confirmed by FISH.

          6. Patients may undergo an optional biopsy of the metastatic disease at baseline and
             after 2 cycles of BIBF-1120.

          7. Estimated life expectancy of at least 3 months

          8. Have ECOG performance status score 0-2

          9. Have received at least one any prior treatment for local recurrence or metastatic
             disease and have relapsed.

         10. Signed and dated written informed consent prior to admission to the study

         11. If Patients have been treated with anti-VEGF agents, such as Bevacizumab, last dose
             must be >/= 4 weeks.

         12. Have tissues from a biopsy, or have up to 20 unstained slides available from archived
             metastatic tissue block for biomarker evaluation

         13. Patients are able to swallow and retain oral medication

        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