Breast Cancer
Conditions
Keywords
stage II breast cancer, stage IIIA breast cancer, stage IIIB 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 more than one drug may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different regimens of combination chemotherapy and comparing them to see how well they work in treating patients with high-risk primary stage II or stage III breast cancer.
Detailed description
OBJECTIVES: * Compare the toxic effects of doxorubicin, cyclophosphamide, and paclitaxel vs cyclophosphamide, thiotepa, and carboplatin in patients with high-risk primary breast cancer. (Arm I closed to accural as of 4/6/2006.) * Compare the efficacies of these regimens followed by peripheral blood stem cell rescue in these patients. * Determine the efficacy of a bisphosphonate to prevent relapse/metastasis after high-dose chemotherapy in these patients. OUTLINE: This is a randomized study. Patients are stratified by stage of disease. Peripheral blood stem cells (PBSC) are collected after mobilization with filgrastim (G-CSF), administered subcutaneously or IV, twice daily beginning 3 days before collection and continuing until collection is complete. All patients receive conventional-dose adjuvant chemotherapy, probably comprising doxorubicin IV, cyclophosphamide IV, and fluorouracil IV over 1 hour on days 1, 22, 43, and 64. Patients are then randomized to receive 1 of 2 treatment arms of high-dose chemotherapy. (Arm I closed to accrual as of 4/6/2006.) * Arm I (ACT) (closed to accrual as of 4/6/2006): Patients receive doxorubicin IV over 24 hours on days -9 to -6, cyclophosphamide IV over 2 hours on day -5, and paclitaxel IV over 24 hours on day -2. PBSC are reinfused on days -2 and 0. G-CSF is administered beginning on day 0 and continuing until blood counts recover. * Arm II (STAMP V): Patients receive cyclophosphamide IV, carboplatin IV, and thiotepa IV over 24 hours on days -7 to -4. PBSC are reinfused and G-CSF is administered as in arm I. Within 4-6 weeks of day 0 of high-dose chemotherapy, patients with estrogen and/or progesterone receptor positive tumors receive oral tamoxifen twice daily for 5 years. Patients are also randomized to receive a bisphosphonate comprising pamidronate IV every 4 weeks for 2 years. Quality of life is assessed before therapy, at 30 days after high-dose chemotherapy, and at 6 and 12 months. Patients are followed every 3 months for 1 year and then every 6 months for at least 10 years. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 3 years.
Interventions
BIOLOGICALfilgrastim
Given IV or subcutaneously
DRUGcarboplatin
Given IV
DRUGcyclophosphamide
Given IV
DRUGdoxorubicin hydrochloride
Given IV
DRUGpaclitaxel
Given IV
DRUGthiotepa
Given IV
PROCEDUREperipheral blood stem cell transplantation
Patients receive autologous peripheral blood stem cells
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 60 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically proven high-risk primary breast cancer with less than 60% chance of progression-free survival of 3 years from diagnosis * Stage II with at least 10 positive axillary nodes OR * Stage IIIA or IIIB * No histologically proven bone marrow metastasis * No CNS metastasis * Hormone receptor status: * Hormone receptor status known PATIENT CHARACTERISTICS: Age: * Physiological age 60 or under Menopausal status: * Not specified Performance status: * Karnofsky 80-100% Life expectancy: * See Disease Characteristics Hematopoietic: * Neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin no greater than 1.5 mg/dL * SGOT or SGPT no greater than 2 times upper limit of normal * Hepatitis B antigen negative Renal: * Creatinine no greater than 1.2 mg/dL * Creatinine clearance at least 70 mL/min * No prior hemorrhagic cystitis Cardiovascular: * Ejection fraction at least 55% by MUGA * No prior significant valvular heart disease or arrhythmia Pulmonary: * FEV\_1 at least 60% of predicted * pO\_2 at least 85 mm Hg on room air * pCO\_2 at least 43 mm Hg on room air * DLCO at least 60% lower limit of predicted Other: * No other prior malignancy except squamous cell or basal cell skin cancer or stage I or carcinoma in situ of the cervix * No CNS dysfunction that would preclude compliance * HIV negative * No sensitivity to E. coli-derived products * Not pregnant * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * At least 4 weeks since prior chemotherapy * No prior doxorubicin of total dose exceeding 240 mg/m\^2 * No prior paclitaxel of total dose of at least 750 mg/m\^2 * No more than 12 months since prior conventional-dose adjuvant chemotherapy Endocrine therapy: * At least 4 weeks since prior hormonal therapy Radiotherapy: * At least 4 weeks since prior radiotherapy * No prior radiation to the left chest wall Surgery: * Not specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Five-Year Relapse-free Survival | Five years | RFS events included death or disease recurrence. Patients who did not experience disease recurrence or death were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Five-Year Overall Survival | Five Years | Patients who were still alive were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (ACT) Patients receive 41.25 mg/m2 of doxorubicin IV over 24 hours on days -9 to -6, 100 mg/kg of cyclophosphamide IV over 2 hours on day -5, and 725 mg/m2 of paclitaxel IV over 24 hours on day -4. PBSC are reinfused on days -2 and 0. G-CSF at 5 ug/kg IV is administered beginning on day 0 and continuing until blood counts recover.
filgrastim: Given IV or subcutaneously
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
paclitaxel: Given IV
peripheral blood stem cell transplantation: Patients receive autologous peripheral blood stem cells | 21 |
| Arm II (STAMP V) Patients receive cyclophosphamide 1.5 g/m2/day IV, carboplatin 200 mg/m2/day IV, and thiotepa 125 mg/m2/day IV over 24 hours on days -7 to -4. PBSC are reinfused on day -2 and 0 and G-CSF at 5ug/kg IV is administered as in arm I.
filgrastim: Given IV or subcutaneously
carboplatin: Given IV
cyclophosphamide: Given IV
thiotepa: Given IV
peripheral blood stem cell transplantation: Patients receive autologous peripheral blood stem cells | 51 |
| Total | 72 |
Baseline characteristics
| Characteristic | Arm I (ACT) | Arm II (STAMP V) | Total |
|---|---|---|---|
| Age, Continuous | 42 years | 51 years | 50 years |
| Region of Enrollment United States | 21 participants | 51 participants | 72 participants |
| Sex: Female, Male Female | 21 Participants | 51 Participants | 72 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 | — / — | — / — |
| other Total, other adverse events | 21 / 21 | 50 / 51 |
| serious Total, serious adverse events | 0 / 21 | 0 / 51 |
Outcome results
Primary
Five-Year Relapse-free Survival
RFS events included death or disease recurrence. Patients who did not experience disease recurrence or death were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method.
Time frame: Five years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (ACT) | Five-Year Relapse-free Survival | 47 percentage of participants |
| Arm II (STAMP V) | Five-Year Relapse-free Survival | 55 percentage of participants |
Secondary
Five-Year Overall Survival
Patients who were still alive were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method.
Time frame: Five Years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (ACT) | Five-Year Overall Survival | 63 percentage of participants |
| Arm II (STAMP V) | Five-Year Overall Survival | 75 percentage of participants |