Abraxane With or Without Tigatuzumab in Patients With Metastatic, Triple Negative Breast Cancer
Condition: Breast Cancer; Triple Negative Breast Cancer; Stage IV Breast Cancer; Metastatic Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Abraxane alone; Abraxane + Tigatuzumab
Intervention description: 100 mg/m2 weekly X 3 doses (Days 1, 8, 15) at 28-day intervals until disease progression or unacceptable toxicity. Abraxane will be administered on an outpatient basis by an IV infusion over 30 minutes. Patients will be evaluated for response every 2 cycles (every 8 weeks).; Tigatuzumab will be administered as a loading dose of 10 mg/kg on Day 1, then 5 mg/kg on Day 15 and then every other week on Days 1 and 15 of subsequent cycles. It will be given as an IV infusion over 60 minutes or less. No dose reductions will be allowed. Tigatuzumab will be administered in combination with the Abraxane according to the intervention described for it.
Intervention MeSH terms: Albumin-Bound Paclitaxel; Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Triple negative breast cancer (TNBC); Metastatic breast cancer; Tigatuzumab (CS-1008); Abraxane (ABI-007); HER-2-neu negative; ER negative, PR negative

Summary:

      Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer
      deaths in American women. Metastatic disease including metastatic breast cancer unfortunately
      remains incurable. One reason is due to the inability to develop specific therapies for
      specific cancer subsets.

      The use of modern genomic techniques has significantly enhanced our recent understanding of
      breast cancer biology. Five distinct breast cancer subsets have been recognized, one of which
      is basal-like breast cancer. Basal-like breast cancer is typically estrogen receptor (ER)
      negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2
      (HER-2-Neu) negative. This is referred to as triple negative breast cancer or TBNC. TBNC
      represents a significant proportion of breast cancer patients (10-20%) and has a poor
      prognosis with no targeted approach to therapy as of yet.

      Tigatuzumab is a humanized monoclonal antibody targeting a death receptor on the breast
      cancer cells. Previous studies have shown that combining antibodies with selected
      chemotherapy agents have induced tumor cell death. The hypothesis of this study is to use
      tigatuzumab and combine it with Abraxane to serve as a targeting agent in metastatic TBNC
      patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have pathologically documented Stage IV breast cancer. If blocks
             (paraffin-embedded tissue) from original diagnosis are available, they will be
             obtained to confirm the diagnosis and for correlative studies. Fifteen slides can be
             obtained from the block if the block is not available to be sent or released.

          -  Tumor must be HER-2-neu negative (defined as 0 or 1+ staining by immunohistochemistry
             or gene amplification ratio less than or equal to 2.0, by fluorescent in situ
             hybridization - FISH), estrogen and progesterone receptors negative (<10%).

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded)

          -  Biopsy of a metastatic lesion is not required for protocol entry but all patients with
             reasonably accessible lesions (chest wall, breast, skin, subcutaneous, superficial
             lymph nodes, bones and liver metastases) must agree to biopsy.

               1. Biopsies may be done with local anesthesia or intravenous conscious sedation,
                  according to standard institutional guidelines.

               2. If a biopsy requires general anesthesia, then it is only allowed if acquisition
                  of tissue is necessary for clinical reasons and excess tissue that would
                  otherwise have been discarded is then used for research purposes. If a biopsy
                  requires general anesthesia, then a biopsy of that site for research purposes
                  only, without a coexisting clinical indication is not allowed on this protocol.

               3. Patients with reasonably accessible lesions as described above, who will not
                  agree with the biopsy, will not be enrolled in the trial.

               4. Patients with NO reasonably accessible lesions as described above can be enrolled
                  in the trial.

        Prior Therapy:

          -  There is no restriction as to the number of prior regimens for metastatic disease as
             long as patients have adequate performance status. Patients with no prior chemotherapy
             for metastatic disease and patients who have received prior therapy with taxanes for
             metastatic disease (taxol or taxotere) are eligible. Stratification will be used for
             randomization of these two categories (no prior chemotherapy for metastatic disease or
             prior taxane therapy for metastatic disease).

          -  Chemotherapy treatment prior to enrollment must be discontinued for at least 3 weeks
             prior to study entry.

          -  Patients must have completed radiation therapy at least 7 days prior to beginning
             protocol treatment.

          -  Patients must have recovered from all reversible toxicities related to prior therapy
             before beginning protocol treatment, and may not have any pre- existing
             treatment-related toxicities in excess of grade 1. Patients must have < grade 2
             pre-existing peripheral neuropathy.

          -  Patients may receive bisphosphonates; however, if used, bone lesions may not be used
             for progression or response.

          -  At least 18 years of age (19 in Alabama).

          -  Life expectancy of greater than 12 weeks.

          -  ECOG performance status < or equal to 2.

          -  Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count: > or equal to 1,500/mcL,

               -  Hemoglobin: > or equal to 9 mg/dL,

               -  Platelets: > or equal to 100,000/mcL,

               -  Total bilirubin: < or equal to 1.5 X institutional upper limit of normal,

               -  AST(SGOT)/ALT(SGPT): < or equal to 2.5 X institutional upper limit of normal
                  without liver metastases, OR < or equal to 5 X institutional upper limit of
                  normal if documented liver metastases,

               -  Creatinine: < or equal to 2.0 mg/dL, OR calculated creatinine clearance greater
                  than or equal to 50 mL/min (calculated by the Cockcroft and Gault method).

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Both men and women are eligible.

          -  Use of an effective means of contraception in subjects of child-bearing potential.

          -  Negative serum or urine beta-HCG pregnancy test at screening for patients with
             childbearing potential.

        Exclusion Criteria:

          -  Patients may not be receiving any other investigational agents.

          -  Prior use of Abraxane for metastatic disease or in the adjuvant setting.

          -  Metastatic lesions identifiable only by PET.

          -  Patients may not be receiving concurrent chemotherapy for treatment of metastatic
             disease.

          -  Active brain metastases: evidence of progression < or equal to 3 months after local
             therapy (patients should be asymptomatic and off corticosteroids and anticonvulsants
             for at least 3 months prior to study entry).

          -  Patients with brain metastases must have at least one site of measurable disease
             outside of the central nervous system.

          -  Uncontrolled concurrent illness including, but not limited to, ongoing or active
             infection, history of recent myocardial infarction, symptomatic congestive heart
             failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
             situations that would limit compliance with study requirements.

          -  Pregnant or lactating women are excluded. Because there is an unknown but potential
             risk for adverse events in nursing infants secondary to treatment of the mother,
             breastfeeding should be discontinued if the mother is treated. These potential risks
             may also apply to other agents used in this study.

          -  A prior invasive malignant disease within five years except for skin cancer (squamous
             cell or basal cell carcinoma).

          -  Patients with known history of HIV or Hepatitis B because of potential for added
             toxicity from treatment regimen.

          -  Dementia or altered mental status that would prohibit the understanding of informed
             consent.