Agatolimod and Trastuzumab in Treating Patients With Locally Advanced or Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab; PF03512676; Correlative Studies
Intervention description: IV at 2 mg/kg over 30 minutes on day 1 of each weekly cycle. Patients who have not received trastuzumab for 4 weeks or more will receive a loading dose of 4 mg/kg over 90 minutes day 1 of the first cycle. The dose of trastuzumab will be based on the patient's actual weight at the start of each 4 week treatment cycle.; Patients also receive PF03512676 subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses.; Blood for performing the correlative studies will be drawn on week 1, 2, 6, 12 and 18.
Intervention MeSH terms: Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent breast cancer; stage IV breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; HER2-positive breast cancer; male breast cancer

Summary:

      RATIONALE: Biological therapies, such as agatolimod, may stimulate the immune system in
      different ways and stop tumor cells from growing. Monoclonal antibodies, such as trastuzumab,
      can block tumor growth in different ways. Some block the ability of tumor cells to grow and
      spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
      Giving agatolimod together with trastuzumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving agatolimod together with trastuzumab
      works in treating patients with locally advanced or metastatic breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed breast cancer

               -  Locally advanced or metastatic disease

          -  HER2-overexpressing tumor, defined as 3+ overexpression by IHC and/or HER2 amplified
             by FISH

          -  Non-measurable disease allowed

          -  Achieved partial response, complete response, or stable disease (i.e., no disease
             progression for ≥ 12 weeks) while on trastuzumab (Herceptin®) and chemotherapy,
             hormonal therapy alone, or trastuzumab alone

               -  Last dose of trastuzumab must have been administered within the past 16 weeks

          -  No unstable brain metastases

               -  Patients with brain metastases are eligible provided they have been stable for ≥
                  1 month after surgery or radiotherapy/radiosurgery AND off corticosteroids and
                  anticonvulsants for ≥ 4 weeks

          -  Hormone receptor status unspecified

        PATIENT CHARACTERISTICS:

          -  ECOG(Eastern Cooperative Oncology Group)performance status (PS) 0-2 (Karnofsky PS
             70-100%)

          -  Absolute neutrophil count ≥ 1,500/mm³

          -  Hemoglobin > 8 g/dL (transfusion/epoetin alfa allowed)

          -  Platelet count ≥ 100,000/mm³

          -  Total bilirubin < 1.5 times upper limit of normal (ULN)

          -  AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if known liver metastases)

          -  Creatinine < 2 mg/mL

          -  Ejection fraction ≥ 50% by echocardiogram or MUGA

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception before, during, and for ≥ 3 months
             after completion of study treatment

          -  No ongoing or active infection requiring oral or IV antibiotics

          -  No known autoimmune disorders or antibody-mediated disorders

          -  No known HIV positivity

          -  No known history of hepatitis B or C (active and/or previously treated)

          -  No other malignancies within the past 5 years except nonmelanoma skin cancer or
             cervical cancer in situ

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to study drugs

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  More than 12 weeks since prior chloroquine

          -  More than 4 weeks since prior growth factors

          -  More than 4 weeks since prior systemic corticosteroids

          -  More than 4 weeks since prior chemotherapy, radiotherapy, or monoclonal antibody
             therapy (except trastuzumab)

          -  No prior agatolimod sodium

          -  No prior allogeneic stem cell transplantation

          -  No prior continuous treatment with single-agent trastuzumab for > 6 months

          -  No more than 3 prior chemotherapy regimens for metastatic breast cancer

          -  Any number of prior hormonal therapies allowed

          -  No other concurrent investigational agents or monoclonal antibodies

          -  No other concurrent anticancer agents or therapies

          -  Concurrent bisphosphonates for skeletal metastasis allowed