Laboratory-Treated T Cells After Second-Line Chemotherapy in Treating Patients With HER2/Neu-Negative Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: HER2Bi-armed activated T cells; Cyclophosphamide; Laboratory biomarker analysis
Intervention description: Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.; After recovering from the last cycle of chemotherapy (approx. two-four weeks) patients will be re-staged. If there are no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide; The association between the [18F]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: HER2-negative breast cancer; stage IV breast cancer; recurrent breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Treating a patient's T
      cells in the laboratory may help the T cells kill more tumor cells when they are put back in
      the body. Giving laboratory-treated T cells after chemotherapy may be an effective treatment
      for breast cancer.

      PURPOSE: This phase II trial is studying how well giving laboratory-treated T cells after
      second-line chemotherapy works in treating patients with HER2/neu-negative metastatic breast
      cancer.
    

Eligibility criteria:

        Inclusion:

          -  Metastatic Breast Cancer. Histologically confirmed breast cancer with evidence of
             metastatic disease (need not be biopsy proven) or locally, advanced unresectable
             disease.

          -  Patients with 0-2+ HER2 expression as determined by immunohistochemistry staining
             and/or FISH ratio <2.0, with the above pathologic criteria will be eligible.

          -  Hormone Therapy. Patients on prior hormonal therapy are eligible. Hormonal therapy
             will be stopped 2 weeks prior to leukopheresis. Hormone therapy may be restarted after
             leukopheresis

          -  Patients may have received any number of prior lines of chemotherapy providing
             Leukopheresis is done when the lymphocyte count has recovered to ≥500 cells/mm3 and
             there are no residual chemotoxicities that would prevent leukopheresis.

          -  Patients who have received Radiotherapy are eligible providing Leukopheresis is done
             at least 4 weeks after radiation to the axial skeleton.

          -  Patients who have received prior biological agents are eligible.

          -  Patients with measurable and non-measurable disease are eligible.

          -  Age > or = to 18 years

          -  ECOG 0-1 or Karnofsky > or = to 70%

          -  Life expectancy > or = to 3 months

          -  Patients with treated brain metastases are eligible

          -  Required Laboratory Data Granulocytes > 1,200/mm3 Platelet count > 50,000/μl
             Hemoglobin ≥ 8 gm/dl BUN < 1.5 times normal Serum creatinine < 1.8 mg/dl Creatinine Cl
             ≥50 ml/mm (can be calculated utilizing the Cockcroft & Gault equation: Creatinine
             Clearance (mL/min) = {(140 - Age)} x Wt [kg] (x 0.85 if Female}/ {72 x SCr [mg/dL]}
             Bilirubin < 1.5 times normal ALT, AST and alkaline phosphatase < 5 times upper normal
             Negative HIV Negaitve Hepatitis B surface antigen Negative Hepatitis C serology LVEF ≥
             45% at rest (MUGA or ECHO) PFT-FEV1, DLCO, and FVC ≥ 50% of predicted

          -  Negative serum test for pregnancy, unless male, prior hysterectomy, tubal ligation, or
             postmenopausal. (Note: postmenopausal is defined as age>55 with amenorrhea for >1 year
             or age <55 years with amenorrhea for 2 years and FSH level within postmenopausal range
             of institutional parameters; patients requiring FSH level to determine menopausal
             status need not have this performed and may choose to proceed with serum pregnancy
             testing.)

        Exclusion Criteria

          -  Patients with HER2 overexpression by immunohistochemistry (IHC) or overamplification
             by FISH are not eligible and are defined as follows: IHC staining of 3+ (uniform,
             intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ
             hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH
             ratio (HER2 gene signals to chromosome 17 signals) of more than 2.0.

          -  Patients with a history of another malignancy within 5 years of study entry are not
             eligible (except basal cell skin carcinoma and carcinoma-in-situ of the cervix).

          -  No serious medical or psychiatric illness which prevents informed consent or intensive
             treatment is allowed.

          -  Patients will be ineligible for treatment on this protocol if (prior to protocol
             entry):

               -  There is a history of a recent myocardial infarction (within one year)

               -  There is a history of a past myocardial infarction (more than one year ago) along
                  with current coronary symptoms requiring medications and/or evidence of depressed
                  left ventricular function (LVEF < 45% by MUGA or ECHO)

               -  There is a current history of angina/coronary symptoms requiring medications
                  and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or
                  ECHO)

               -  There is clinical evidence of congestive heart failure requiring medical
                  management (irrespective of MUGA or ECHO results)

          -  Patients will be ineligible if there is recurrent pleural effusion or ascites
             requiring drainage (through thoracentesis, paracentesis, or indwelling device) more
             often than once every 4 weeks.

          -  Patients with clinical evidence of active CNS metastases are ineligible for therapy on
             this protocol.