BAY43-9006 - Phase II in Advanced Breast Cancer
Condition: Breast Neoplasms; Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Sorafenib (Nexavar, BAY43-9006)
Intervention description: Sorafenib 400 mg administered twice daily (b.i.d.)
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer

Summary:

      The purpose of this study is to evaluate the anti-cancer activity and safety of BAY43-9006
      (Sorafenib) in patients, who suffer from an advanced breast tumour, which has spread to other
      organs of body despite treatment that the patient has received so far.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age > 18 years

          -  Women with prior histologically documented diagnosis of breast cancer

          -  Subjects with metastatic disease who have already received and failed at least one
             chemotherapy regimen for metastatic disease and, if ER/PgR +ve, have failed on at
             least adjuvant hormonal therapy

          -  Subjects for whom trastuzumab treatment is not indicated, no longer effective or
             refused by the subjects

          -  Four weeks since the last cytotoxic chemotherapy or clear evidence of progression on
             hormonal therapy

          -  Subjects who have at least one measurable lesion by CT (Computed Tomography) scan or
             MRI (Magnetic Resonance Imaging) according to modified WHO Tumour Response Criteria

          -  Subjects who have an Eastern Co-operative Oncology Group (ECOG) performance status of
             0, 1 or 2

          -  Adequate bone marrow, liver and renal function as assessed by the following laboratory
             evaluations:

               -  Hemoglobin > 9.0 g/dl

               -  Absolute neutrophil count (ANC) > 1,500/mm3

               -  Platelet count = 100,000/µl

               -  Total bilirubin =1.5 x the upper limit of normal.

               -  Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) = 2.5 x upper
                  limit of normal (=5 x upper limit of normal for subjects with liver involvement
                  of their cancer)

               -  Amylase and lipase = 1.5 x the upper limit of normal

               -  Serum creatinine = 3.0 x the upper limit of normal

               -  Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial
                  Thromboplastin Time (PTT) < 1.5 x upper limit of normal (subjects who receive
                  anti-coagulation treatment with an agent such as warfarin or heparin will be
                  allowed to participate provided that no evidence of underlying abnormality in
                  these parameters exists)

          -  Subjects who give written informed consent prior to any study specific screening
             procedures with the understanding that the subject has the right to withdraw from the
             study at any time, without prejudice

          -  Life expectancy of at least 12 weeks

          -  Signed informed consent must be obtained prior to any study specific procedures

        Exclusion Criteria:

          -  Previous malignancy (except for cervical carcinoma in situ, adequately treated basal
             cell carcinoma, or superficial bladder tumours [Ta, Tis and T1] or other malignancies
             curatively treated > 2 years prior to entry)

          -  Congestive heart failure > New York Heart Association (NYHA) Class II

          -  Cardiac arrhythmia requiring anti-arrhythmic (excluding beta blockers or digoxin)

          -  Active coronary artery disease or ischaemia

          -  Active clinically serious bacterial or fungal infections (> grade 2 National Cancer
             Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3)

          -  Known History of Human Immunodeficiency Virus (HIV) infection or chronic hepatitis B
             or C

          -  Metastatic brain or meningeal tumors unless the subject is > 6 months from definitive
             therapy, has a negative imaging study within 4 weeks of study entry and is clinically
             stable with respect to the tumor at the time of study entry. Also the patient must not
             be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable
             provided that the dose is stable for 1 month prior to and following screening
             radiographic study)

          -  Subjects with seizure disorders requiring medication (such as steroid or
             anti-epileptics)

          -  History of organ allograft

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the subject's participation in the study or evaluation of the study results

          -  Known or suspected allergy to the investigational agent

          -  Any condition that is unstable or which could jeopardize the safety of the subject and
             his/her compliance in the study. Pregnant or breast-feeding subjects. Women of
             childbearing potential must have a negative pregnancy test performed within seven days
             prior to the start of study drug. Women enrolled in this trial must use adequate
             barrier birth control measures during the course of the trial.

        Excluded therapies include:

          -  Anti-cancer chemotherapy, hormonal therapy or immunotherapy during the study or within
             4 weeks of study entry. Mytomicin or nitroureas should not be given within 6 weeks of
             study entry

          -  Significant surgery within 4 weeks prior to the start of study drug

          -  Any bone marrow transplant or stem cell rescue within 4 months of the start of study
             drug

          -  Radiotherapy during the study or within 3 weeks of the start of drug

          -  Use of biologic response modifiers, such as Granulocyte-Colony Stimulating Factor
             (G-CSF), within 3 weeks of study entry

          -  Investigational drug therapy outside of this trial during or within 30 days prior to
             start of the study drug

          -  Concomitant treatment with ketoconazole, itraconazole, ritonavir, or use of grapefruit
             juice

          -  Prior use of Raf-Kinase Inhibitors (RKI), Methyl Ethyl Ketone (MEK) or farnesyl
             transferase inhibitors

          -  Concomitant treatment or use of St. John's Wort

          -  Prior use of bevacizumab and all other drugs that target Vascular Endothelial Growth
             Factor (VEGF)/VEGF receptors