TPI 287 in Breast Cancer Metastatic to the Brain
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: TPI 287; Dexamethasone; Benadryl; Ranitidine
Intervention description: Starting dose Phase I: 160 mg/m2 by vein over 60 minutes on Days 1, 8, and 15 of every 28 day cycle.
Starting Dose Phase II: Maximum tolerated dose from Phase I.; 6 mg by mouth at 12 hours and 6 hours prior to treatment. As alternative and based on the treating physician discretion, dexamethasone 10 mg by vein may be given 30-60 minutes prior to treatment with TPI 287.; 12.5-25 mg intravenous (IV) push 30-60 minutes prior; As H2 blocker 1mg/kg IV 30-60 minutes prior
Intervention MeSH terms: Diphenhydramine; Dexamethasone; Ranitidine; Ranitidine bismuth citrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Brain metastases; TPI 287; Computed Tomography; CT; Magnetic Resonance Imaging; MRI

Summary:

      The goal of the first part of this clinical research study is to find the highest tolerable
      dose of TPI-287 in patients with breast cancer that has spread to the brain.

      The goal of the second part of this study is to learn if TPI-287 can control breast cancer
      that has spread to the brain. The safety of this drug will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have histologically proven breast cancer with metastatic disease to the
             brain.

          2. Patients must have measurable disease on MRI that has progressed after prior therapy.
             PD will be defined as a>/= 25% increase in the sum of the products of greatest
             perpendicular diameters of all measurable disease over the smallest sum observed
             (since treatment started) on Gd-MRI, the appearance of new lesions on scan, or
             clinical or neurologic worsening despite stable disease on the last 2 scans.

          3. Patients may have had any number of prior surgeries, radiation and/or chemotherapy
             regimens as adjuvant, neoadjuvant or palliative therapy for the treatment of their
             disease

          4. Patients must be >/=18 years of age.

          5. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0,1 or 2.

          6. Patients must have adequate bone marrow function as evidenced by an absolute
             neutrophil count >/=1,500/microliters and a platelet count >/=100,000/microliter,
             adequate renal function as evidenced by serum creatinine </=2.0 mg/dL, adequate
             hepatic function as evidenced by serum total bilirubin </=2.0 mg/dL, AST/serum
             glutamate oxaloacetate transaminase (SGOT) and ALT/serum glutamate pyruvate
             transaminase (SGPT) </= 3X the upper limit of normal (ULN).

          7. Patients must have recovered and healed from the effects of any prior surgery, must
             have received prior chemotherapy at least 2 weeks prior to dosing with adequate
             recovery of white blood cell count (WBC) and platelet counts, and at least 12 weeks
             must have elapsed from the completion of radiotherapy, unless there are new lesions
             appearing on imaging within this 12 weeks frame.

          8. Women of child-bearing potential (i.e. </= 50 years of age or has had menstrual cycle
             within the past 12 months, if > 50 years of age. If in doubt, check FSH, LH and
             estradiol level) must have a negative urine or serum pregnancy test at screening.

          9. Sexually active patients must agree to use adequate contraception (abstinence or
             barrier contraceptives must be used throughout the trial and one month after end of
             treatment) for the duration of the study .

         10. Patients or their legal representative must be able to read, understand and sign an
             informed consent form (ICF).

         11. TPI 287 may interfere with coumadin dosing and patients who are taking this
             combination will require monitoring of their PT, PTT and international normalized
             ratio (INR).

        Exclusion Criteria:

          1. Patients who are receiving concurrent enzyme-inducing anti-epileptic drugs (EIAEDs)
             (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital and
             primidone) or who received EIAEDs within 2 weeks prior to the first dose of study
             drug.

          2. Patients with uncontrolled intracranial hypertension syndrome (defined as: persistence
             of headache, transient visual obscurations, and/or diplopia despite optimal clinical
             management) or uncontrolled seizure activity (i.e. recorded despite optimal medical
             management).

          3. Patients who are not on a stable or decreasing steroid dose for the previous week
             prior to the first dose of study enrollment

          4. Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks
             for treatment of their brain metastases

          5. Patients with an active infection (i.e., clinical signs or symptoms, including, but
             not limited to: bleeding/pustulant skin infections; productive cough associated with
             fever) on antibiotics or with a fever >/=38.5°C within 3 days prior to registration
             (i.e. date when the patient signs the consent and/or the patient is registered in
             CORE).

          6. Patients with New York Heart Association (NYHA) Class 3 or 4 congestive heart failure.

          7. Patients with known HIV or Hepatitis B or C

          8. Patients who are pregnant or lactating or not practicing adequate contraception

          9. Patients with any other medical condition, including mental illness or substance
             abuse, deemed by the Investigator to be likely to interfere with the patient's ability
             to sign the ICF or his/her ability to cooperate and participate in the study, or to
             interfere with the interpretation of the results.

         10. Patients who are receiving concomitant systemic therapy for breast cancer.

         11. Patients with leptomeningeal disease (LMD) or with a history of LMD will be excluded.