Combination Chemotherapy With or Without Trastuzumab Followed By an Autologous Stem Cell Transplant and Radiation Therapy in Treating Patients With Stage III or Stage IV Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: trastuzumab; carboplatin; cyclophosphamide; melphalan; thiotepa; adjuvant therapy; autologous-autologous tandem hematopoietic stem cell transplantation; bone marrow ablation with stem cell support; radiation therapy
Intervention description: Cycle 1: 6 mg/kg on day -2 from PBSC reinfusion Cycle 2: 6 mg/kg on day -7 from PBSC reinfusion; Cycle 2: 800 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion; Cycle 2: 6000 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion; Cycle 1: 150 mg/m2 on day -1 from PBSC reinfusion; Cycle 2: 500 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion; Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation and helical tomotherapy or loco-regional radiotherapy.; Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation.; Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation; After recovery from high-dose chemotherapy and autologous PBSC transplantation; patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Treatment should be delivered daily M-F @ 180-200 cGY/day to a total of 4,500 to 5,040 cGy.
Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites. Treatment should be delivered daily @180-220 cGY/day to a total of 4,000-5,000 cGy.
Intervention MeSH terms: Cyclophosphamide; Melphalan; Thiotepa; Carboplatin; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Maximum age: 65 Years
Healthy volunteers: No
Keywords: stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; inflammatory breast cancer; male breast cancer; recurrent breast cancer; invasive ductal breast carcinoma with predominant intraductal component; invasive ductal breast carcinoma; medullary ductal breast carcinoma with lymphocytic infiltrate; mucinous ductal breast carcinoma; Paget disease of the breast with invasive ductal carcinoma; papillary ductal breast carcinoma; tubular ductal breast carcinoma; invasive lobular breast carcinoma with predominant in situ component; invasive lobular breast carcinoma; comedo ductal breast carcinoma

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. 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. An autologous stem cell transplant may be able to replace
      blood-forming cells that were destroyed by chemotherapy. Radiation therapy uses high-energy
      x-rays to kill tumor cells. Giving combination chemotherapy with or without trastuzumab
      followed by an autologous stem cell transplant and radiation therapy may kill more tumor
      cells.

      PURPOSE: This phase II trial is studying how well giving combination chemotherapy with or
      without trastuzumab followed by an autologous stem cell transplant and radiation therapy
      works in treating patients with stage III or stage IV breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed breast cancer, meeting 1 of the following stage criteria:

               -  Stage IIIB or IIIC disease, meeting both of the following criteria:

                    -  Must have received prior neoadjuvant or adjuvant therapy

                    -  Must have undergone lumpectomy or mastectomy

               -  Stage IV disease, meeting all of the following criteria:

                    -  Only 1-3 organ sites with disease involvement after induction chemotherapy

                    -  Achieved at least a partial response after induction chemotherapy

                    -  No more than 3 lesions in the organ sites combined

          -  Inflammatory breast cancer allowed

          -  Completed chemotherapy, surgery, or radiotherapy for breast cancer within the past 6
             months

          -  Hormone receptor status:

               -  Not specified

        PATIENT CHARACTERISTICS:

        Age

          -  65 and under

        Sex

          -  Male or female

        Menopausal status

          -  Not specified

        Performance status

          -  Karnofsky 80-100%

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Absolute neutrophil count ≥ 1,000/mm^3

          -  Platelet count ≥ 100,000/mm^3

        Hepatic

          -  SGOT or SGPT ≤ 2 times upper limit of normal

          -  Bilirubin ≤ 1.5 mg/dL

        Renal

          -  Creatinine ≤ 1.2 mg/dL

          -  Creatinine clearance ≥ 70 mL/min

        Cardiovascular

          -  LVEF ≥ 55% by MUGA or echocardiogram

        Pulmonary

          -  FEV_1 ≥ 60% of predicted

          -  DLCO ≥ 60% of the lower limit of predicted value

          -  Oxygen saturation > 92% on room air

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No autoimmune disorders

          -  No immunosuppressive condition

          -  No other malignancy within the past 5 years

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  No prior biologic therapy except trastuzumab (Herceptin®)

        Chemotherapy

          -  See Disease Characteristics

        Endocrine therapy

          -  Not specified

        Radiotherapy

          -  See Disease Characteristics

          -  No prior radiotherapy to adjacent or involved sites of disease that would preclude
             study radiotherapy

        Surgery

          -  See Disease Characteristics

        Other

          -  No other concurrent anticancer therapy