TKI258 for Metastatic Inflammatory Breast Cancer Patients
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Inflammatory Breast Neoplasms
Intervention: Dovitinib
Intervention description: 500 mg by mouth for 5 consecutive days, followed by a 2-day rest period (5 days on/2 days off schedule) for every 28 day cycle.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic inflammatory breast cancer; Stage IV disease; HER2-negative; Dovitinib; TKI258

Summary:

      The goal of this clinical research study is to learn if dovitinib can help to control
      inflammatory breast cancer. The safety of this drug will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients 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 for diagnosis.

          2. Patients have stage IV disease with local or distant relapse

          3. Patients have negative HER2 expression by IHC (defined as 0 or1+), or fluorescence in
             situ hybridization (FISH). If HER2 is 2+, negative HER2 expression must be confirmed
             by FISH.

          4. Patients are able to swallow and retain oral medication.

          5. Patients have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          6. Patients have received two or more standard chemotherapies for metastatic disease and
             have relapsed.

          7. Patients have ability and willingness to sign written informed consent.

          8. Patients are 18 years of age or older.

          9. Female patients of childbearing potential (A female not free from menses > 2 years or
             not surgically sterilized) must be willing to use highly effective contraception to
             prevent pregnancy or agree to abstain from heterosexual activity throughout the study.
             Highly effective contraception, defined as male condom with spermicide, diaphragm with
             spermicide, intra-uterine device. Highly effective contraception must be used by both
             sexes during the study and must be continued for 8 weeks after the end of study
             treatment. Oral, implantable, or injectable contraceptives may be affected by
             cytochrome P450 interactions, and are therefore not considered effective for this
             study.

         10. Female patients of childbearing potential must have negative serum pregnancy test
             </=14 days prior to starting study treatment.

         11. If Patients have been treated with anti-vascular endothelial growth factor (VEGF)
             agents, such as Bevacizumab, last dose must be > 4 weeks.

         12. Patients have biopsy tissue of the metastatic disease (including chest wall or
             regional nodes) available (paraffin blocks or up to 20 unstained slides), if no biopsy
             tissue available, a biopsy (or thoracentesis if patient has pleural effusion only) of
             the metastatic disease will be performed to confirm the diagnoses.

         13. Serum total bilirubin must be within Upper Limited Normal (T. Bilirubin upper limit of
             normal (ULN)=1.0 mg/dl)

         14. AST and ALT must be < 2.5 x ULN(with or without liver metastases).

        Exclusion Criteria:

          1. Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy,
             radiation therapy and biological therapy) while taking study medication.

          2. Cirrhosis of liver, or known hepatitis B or C infection have hepatic impairment
             Child-Pugh Score of B or worse.

          3. Absolute neutrophil count (ANC) < 1.5

          4. Patients have an active infection and require IV or oral antibiotics.

          5. 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) left ventricular ejection fraction (LVEF) assessed by 2-D
             echocardiogram (ECHO) < 50% or lower limit of normal (which ever is higher) or
             multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (which ever is
             higher). d) 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), Cerebrovascular Accident (CVA), Transient Ischemic
             Attack (TIA), Pulmonary Embolism (PE); e) Uncontrolled hypertension defined by an
             SBP>150 and/or a diastolic blood pressure (DBP)>100 mm Hg with or without
             anti-hypertensive medication.

          6. History of gastrointestinal disorders (medical disorders or extensive surgery) which
             may interfere with the absorption of the study drug.

          7. 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.

          8. Patients with only locally or regionally confined disease without evidence of
             metastatic disease.