Breast Cancer
Conditions
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
Brief 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.
Detailed description
OBJECTIVES: * Determine the feasibility of 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 in patients with high-risk stage IIIB, IIIC, or IV breast cancer. * Determine the toxic effects of this regimen in these patients. OUTLINE: Patients undergo stem cell collection. * Course 1: Patients receive high-dose melphalan IV with or without trastuzumab (Herceptin®). One day later, patients undergo autologous peripheral blood stem cell (PBSC) transplantation. No more than 7 weeks later, patients proceed to course 2. * Course 2: Patients receive high-dose carboplatin, thiotepa, and cyclophosphamide IV continuously over 4 days followed by autologous PBSC transplantation. After recover from high-dose chemotherapy and autologous PBSC transplantation, patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Interventions
BIOLOGICALtrastuzumab
Cycle 1: 6 mg/kg on day -2 from PBSC reinfusion Cycle 2: 6 mg/kg on day -7 from PBSC reinfusion
DRUGcarboplatin
Cycle 2: 800 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
DRUGcyclophosphamide
Cycle 2: 6000 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
DRUGmelphalan
Cycle 1: 150 mg/m2 on day -1 from PBSC reinfusion
DRUGthiotepa
Cycle 2: 500 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
PROCEDUREadjuvant therapy
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.
PROCEDUREbone marrow ablation with stem cell support
Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation
RADIATIONradiation therapy
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.
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 65 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 5-Year Relapse-free Survival Rate | From time of initial PBPC rescue until death or disease recurrence (disease progression for patients with stage IV disease), whichever came first, up to 5 years post treatment | Estimated using the product-limit method of Kaplan and Meier. Relapse defined as appearance of any new lesions during or after protocol treatment. Whenever possible, relapses should be documented histologically. |
| 5-Year Overall Survival Rate | From time of initial PBPC rescue until the date of death from any cause, assessed up to 5 years post treatment. | Estimated using the product-limit method of Kaplan and Meier. Patients who were still alive were censored at the date of last follow-up |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients Patients undergo stem cell collection. Patients receive high-dose melphalan IV with or without trastuzumab (Herceptin®), one day later, patients undergo autologous peripheral blood stem cell (PBSC) transplantation, no more than 7 weeks later, patients proceed to course 2; OR Patients receive high-dose carboplatin, thiotepa, and cyclophosphamide IV continuously over 4 days followed by autologous PBSC transplantation. After recover from high-dose chemotherapy and autologous PBSC transplantation, patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites. | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 47 years |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 32 |
| serious Total, serious adverse events | 24 / 32 |
Outcome results
Primary
5-Year Overall Survival Rate
Estimated using the product-limit method of Kaplan and Meier. Patients who were still alive were censored at the date of last follow-up
Time frame: From time of initial PBPC rescue until the date of death from any cause, assessed up to 5 years post treatment.
Population: Patients from this study were combined with patients from a follow-up study in which 27 patients from this study met the eligibility requirements for meta-analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Patients | 5-Year Overall Survival Rate | 75 percentage of participants |
Primary
5-Year Relapse-free Survival Rate
Estimated using the product-limit method of Kaplan and Meier. Relapse defined as appearance of any new lesions during or after protocol treatment. Whenever possible, relapses should be documented histologically.
Time frame: From time of initial PBPC rescue until death or disease recurrence (disease progression for patients with stage IV disease), whichever came first, up to 5 years post treatment
Population: Patients from this study were combined with patients from a follow-up study in which 27 patients from this study met the eligibility requirements for meta-analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Patients | 5-Year Relapse-free Survival Rate | 53 percentage of participants |