Phase II Study of Ixabepilone in Metastatic Breast Cancer and Its Effects on the Ultrastructure of Neurons
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: ixabepilone
Intervention description: ixabepilone 40 mg/m2 Q3w over 3 hours
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: breast

Summary:

      Primary Objectives

        -  Assess ultrastructure changes in dermal myelinated nerves of patients who receive
           ixabepilone chemotherapy

        -  Detailed characterization of peripheral neuropathy in patients who receive ixabepilone

      Secondary Objectives

        -  Clinical benefit rate

        -  Time to progression ( TTP)

        -  Toxicity

        -  Exploratory studies:

             -  Relation of MDR 1 and TRKA polymorphisms to evolution of ultrastructural neurologic
                changes observed in neurons.

             -  Relation of NGF, IL8, and IL10 to the development of clinical symptoms and
                ultrastructural changes in neurons.
    

Eligibility criteria:

        Inclusion Criteria

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Histologic or cytologic diagnosis of adenocarcinoma originating in the breast.

          -  Evidence that the cancer is metastatic or locally advanced and not curable by local
             measures (i.e., surgery, radiation).

        NOTE: There is no limit on number of prior chemotherapy regimens received.

          -  Karnofsky performance status (KPS) score of 70 - 100; (Appendix 1).

          -  Life expectancy of at least 12 weeks.

          -  Adequate recovery of drug related toxicities from prior systemic therapy (recovery to
             < = Grade 1 except for Grade 2 fatigue and alopecia).

          -  Adequate recovery from recent surgery and radiation therapy. At least one week must
             have elapsed from the time of a minor surgery and/or focal/palliative radiation
             therapy; at least 3 weeks for major surgery and other radiation therapy.

          -  Women or Men, age > = 18 years.

          -  Patients must have normal organ and marrow function as defined below:

               -  Hematologic function with absolute neutrophils ≥ 1,500/mm3 and/or platelets >
                  125,000/mm3

               -  Hepatic function with serum bilirubin less than 1.5 times the upper institutional
                  limits of normal, ALT ≤ 2.5 times the upper institutional limits of normal (≤ 5
                  times the upper institutional limits of normal if documented hepatic metastases
                  are present)

               -  Renal function with serum creatinine ≤ 1.5 times the upper limit of normal

          -  Women of childbearing potential (WOCBP) and men with partners who are of childbearing
             potential must be using an adequate method of contraception to avoid pregnancy
             throughout the study and for up to 4 weeks after the study in such a manner that the
             risk of pregnancy is minimized.

        WOCBP include any female who has experienced menarche and who has not undergone successful
        surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy)
        or is not postmenopausal (defined as amenorrhea > = 12 consecutive months; or women on
        hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH)
        level > 35 mIU/mL). Even women who are using oral, implanted or injectable contraceptive
        hormones or mechanical products such as an intrauterine device or barrier methods
        (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where
        partner is sterile (e.g., vasectomy), should be considered to be of child bearing
        potential.

        - WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or
        equivalent units of HCG) within 72 hours prior to the start of study medication.

        Should a woman become pregnant or suspect she is pregnant while participating in this
        study, she should inform her treating physician immediately.

        Exclusion Criteria

          -  Patients with known and active brain and/or leptomeningeal metastases should be
             excluded from this clinical trial because of their poor prognosis and because they
             often develop progressive neurologic dysfunction that would confound the evaluation of
             neurologic and other adverse events.

          -  CTC Grade 2 or greater neuropathy (motor or sensory) at study entry.

          -  Prior treatment with ixabepilone.

          -  Serious intercurrent infections, or nonmalignant medical illnesses that are
             uncontrolled or whose control may be jeopardized by the complications of this therapy,
             including, but not limited to: ongoing or active infection, symptomatic congestive
             heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  Known history of HIV infection.

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier.

          -  Patients may not be receiving any other concurrent chemotherapy, hormonal therapy,
             immunotherapy regimens or radiation therapy, standard or investigational.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ixabepilone.

          -  Known prior severe hypersensitivity reactions to agents containing CremophorEL.

          -  Patients may not be receiving any prohibited therapies and/or medications.

          -  Pregnant and lactating women are excluded from the study because the risks to an
             unborn fetus or potential risks in nursing infants are unknown.