Breast Cancer
Conditions
Keywords
stage IIIB breast cancer, inflammatory breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase II trial is studying how well chemotherapy and stem cell transplantation work in treating patients with stage IIIB breast cancer.
Detailed description
OBJECTIVES: * Determine the effectiveness of neoadjuvant dose intensive sequential chemotherapy, followed by surgical resection, adjuvant therapy, and tandem high dose chemotherapy and stem cell rescue in patients with inflammatory stage IIIB breast cancer. * Determine the clinical and pathological remission rate (complete, partial, and overall) following neoadjuvant dose dependent sequential chemotherapy in patients with inflammatory stage IIIB breast cancer. * Determine the relapse and survival rate of these patients with the above therapy. * Determine the potential correlations between inflammatory features and hereditary background. OUTLINE: Patients are stratified according to those who have had no more than 1 cycle of neoadjuvant chemotherapy (stratum 1) and those who have had more than 1 cycle of neoadjuvant chemotherapy and/or modified radical mastectomy (stratum 2). Patients in stratum 1 receive doxorubicin IV over 96 hours on days 1-4, 15-19, and 29-32. Paclitaxel is infused over 96 hours on days 43-47 and 57-60. Filgrastim (G-CSF) is administered on days 5-10, 20-25, 33-38, 48-55, and 61-68, and beyond if the granulocyte count is less than 1000/mm\^3. A modified radical mastectomy is performed between days 70 and 80. All stratum 1 and stratum 2 patients then receive paclitaxel IV for 96 hours on days 100-104, and cyclophosphamide IV on day 121. Filgrastim is administered at one dose on days 105-110 and days 122-127 and at a higher dose on days 110-116 and days 128-135. Stem cells are harvested from the patient on days 113-116 and days 132-135. High-dose chemotherapy is then administered to all patients in the study. Course 1 starts with doxorubicin IV on days -7 to -3. Paclitaxel IV is administered for 24 hours on day -2. Filgrastim is administered by IV on day -1 and continued until the granulocyte count is greater than 1000/mm\^3 for 3 days. Peripheral stem cells are reinfused on day 0. Course 2 starts 4-6 weeks after the start of course 1 with melphalan and cisplatin being infused on day -11. Filgrastim is administered IV on days -10 to -6. Melphalan and cisplatin are administered again on day -4. Stem cells are infused on day -3 and on day 0. Filgrastim is then administered until the granulocyte count is at least 1000/mm\^3 for 3 days. Radiation therapy is started 4-7 weeks after the beginning of course 2. Tamoxifen is started within 2 weeks of discharge following course 2 in patients with hormone receptor positive tumors. Patients are followed every 3 months for two years and then annually for the next three years. PROJECTED ACCRUAL: Approximately 60 patients will be accrued, at a rate of about 15 per year.
Interventions
BIOLOGICALfilgrastim
DRUGcisplatin
DRUGcyclophosphamide
DRUGdoxorubicin hydrochloride
DRUGmelphalan
DRUGmesna
DRUGpaclitaxel
DRUGtamoxifen citrate
PROCEDUREbone marrow ablation with stem cell support
PROCEDUREconventional surgery
PROCEDUREperipheral blood stem cell transplantation
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically proven stage IIIB breast cancer with dermal/epidermal invasion or clinical features of inflammation, erythema, pain or hypersensitivity, edema, or thickening of the skin * Diagnosis within the past 6 months PATIENT CHARACTERISTICS: Age: * 60 and under Performance status: * Karnofsky 80-100% Life expectancy: * Not specified Hematopoietic: * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin less than 1.5 mg/dL * SGOT or SGPT no greater than 1.5 times the upper limit of normal Renal: * Creatinine less than 1.2 mg/dL * Creatinine clearance at least 80 mL/min * No history of hemorrhagic cystitis Cardiovascular: * Left ventricular fraction at least 55% on MUGA scan * No previous valvular heart disease or arrhythmia Pulmonary: * FEV\_1 at least 60% predicted * Room air pO\_2 greater than 85 mmHg * Room air pCO\_2 no greater than 43 mmHg * DLCO at least 60% of the lower limit of predicted value Other: * No history of malignant disease in the past 5 years, except for squamous or basal cell skin cancer and stage I or in situ cervical cancer * No organic CNS dysfunction * Not pregnant * No known and potentially disabling psychosocial history * Not positive for hepatitis B or HIV PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * Stratum 1: * No more than one cycle of chemotherapy * Stratum 2: * No greater than 225 mg/m\^2 doxorubicin and no greater than 250 mg/m\^2 paclitaxel during previous chemotherapy Endocrine therapy: * Not specified Radiotherapy: * No prior radiation to the left chest wall Surgery: * Modified radical mastectomy allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Five-year Overall Survival | From date of mastectomy until date of death, 5 years post mastectomy. | Estimated using the product-limit method of Kaplan and Meier. Endpoint is defined as death due to any cause. |
| Three-year Relapse-free Survival | From date of mastectomy until date of relapse or death from any cause, 3 years post mastectomy. | Estimated using the product-limit method of Kaplan and Meier. Relapse defined as appearance of any new lesions during or after protocol treatment. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORGeorge Somlo, MD
City of Hope Medical Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neoadjuvant Chemo Followed by Surgery & High-dose Chemo With PSC Rescue Patients receive chemotherapy, surgical removal of the cancer followed by additional chemotherapy, followed by two treatment cycles of very high-dose chemotherapy, return of bone marrow derived cells, followed by radiation therapy and if indicated five years of tamoxifen treatment.
filgrastim
cisplatin
cyclophosphamide
doxorubicin hydrochloride
melphalan
mesna
paclitaxel
tamoxifen citrate
bone marrow ablation with stem cell support
conventional surgery
peripheral blood stem cell transplantation | 14 |
| High-dose Chemo With Rescue Following surgery patients receive chemotherapy, followed by two treatment cycles of very high-dose chemotherapy, return of bone marrow derived cells, followed by radiation therapy and if indicated five years of tamoxifen treatment.
filgrastim
cisplatin
doxorubicin hydrochloride
melphalan
mesna
paclitaxel
tamoxifen citrate
bone marrow ablation with stem cell support
peripheral blood stem cell transplantation | 27 |
| Total | 41 |
Baseline characteristics
| Characteristic | High-dose Chemo With Rescue | Neoadjuvant Chemo Followed by Surgery & High-dose Chemo With PSC Rescue | Total |
|---|---|---|---|
| Age, Continuous | 50 years | 49 years | 50 years |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 13 Participants | 38 Participants |
| Region of Enrollment United States | 27 Participants | 14 Participants | 41 Participants |
| Sex: Female, Male Female | 27 Participants | 14 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 14 | 14 / 27 |
| other Total, other adverse events | 13 / 14 | 23 / 27 |
| serious Total, serious adverse events | 0 / 14 | 2 / 27 |
Outcome results
Primary
Five-year Overall Survival
Estimated using the product-limit method of Kaplan and Meier. Endpoint is defined as death due to any cause.
Time frame: From date of mastectomy until date of death, 5 years post mastectomy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant Chemo Followed by Surgery & High-dose Chemo With PSC Rescue | Five-year Overall Survival | 69.2 percentage of participants |
| High-dose Chemo With Rescue | Five-year Overall Survival | 70.4 percentage of participants |
Primary
Three-year Relapse-free Survival
Estimated using the product-limit method of Kaplan and Meier. Relapse defined as appearance of any new lesions during or after protocol treatment.
Time frame: From date of mastectomy until date of relapse or death from any cause, 3 years post mastectomy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant Chemo Followed by Surgery & High-dose Chemo With PSC Rescue | Three-year Relapse-free Survival | 61.5 percentage of participants |
| High-dose Chemo With Rescue | Three-year Relapse-free Survival | 77.8 percentage of participants |