Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer
Conditions
Brief summary
This phase II trial studies the side effects and how well giving cyclophosphamide and paclitaxel with or without trastuzumab works in treating patients with stage I-II breast cancer who have undergone surgery. Drugs used in chemotherapy, such as cyclophosphamide and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody therapy, such as trastuzumab, with chemotherapy may kill more tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery.
Detailed description
PRIMARY OBJECTIVES: I. To determine the toxicities and ability to complete the planned treatment of a dose-dense regimen of cyclophosphamide and paclitaxel with or without trastuzumab in patients with newly diagnosed stage I-II breast cancer. II. To estimate recurrence free survival of a dose-dense regimen of cyclophosphamide and paclitaxel with or without trastuzumab in patients with newly diagnosed stage I-II breast cancer. OUTLINE: SYSTEMIC CHEMOTHERAPY: Patients receive cyclophosphamide intravenously (IV) over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY (human epidermal growth factor receptor 2 \[Her-2\] neu positive patients): Patients receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 5 courses and then every 21 days for 14 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 3 years.
Interventions
DRUGcyclophosphamide
Given IV
DRUGpaclitaxel
Given IV
BIOLOGICALtrastuzumab
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
University of Nebraska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed newly diagnosed stage I-II breast cancer * Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment * Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Absolute neutrophil count greater than or equal to 1,500/mcl * Platelet count equal to or greater than 150,000/mcl * Hemoglobin \> 11 gm/dl * Alkaline phosphatase equal or less than 1.5 times the upper limit of normal (ULN) * Total bilirubin equal to or less than 1.5 times the ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times the ULN * Creatinine less than 1.5 times the ULN * Able to give informed consent * All included patients must have normal cardiac function as defined by an ejection fraction of \> 50% by echocardiogram * Able to return for treatment and follow-up on the specified days
Exclusion criteria
* Prior malignancy; except for adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas * Patients with preexisting grade II peripheral neuropathy * Patients with prior chemotherapy * Stage IV or metastatic breast cancer * Pregnant or nursing women * Inability to cooperate with treatment protocol * No active serious infections or other conditions precluding chemotherapy * Any comorbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol (e.g. unstable angina, myocardial infarction within 6 months, severe infection, etc.) * Known hypersensitivity to any component of required drugs in the study * Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C or active hepatitis * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiograph (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-free Survival | Time from the start of treatment to recurrence, second malignancy, or death as a first event, assessed up to 3 years | Recurrence-free survival curves will be plotted for subjects treated with stage I and II disease. |
Countries
United States
Participant flow
Pre-assignment details
Of the 112 subjects consented for this study, 3 were ineligible, 9 withdrew before study treatment starting. Only 100 subjects treated were available for analysis.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Chemotherapy With or Without Maintenance Therapy) SYSTEMIC CHEMOTHERAPY: Patients receive cyclophosphamide IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY (Her-2 neu positive patients): Patients receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 5 courses and then every 21 days for 14 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide, paclitaxel, trastuzumab: Given IV | 112 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
Baseline characteristics
| Characteristic | Treatment (Chemotherapy With or Without Maintenance Therapy) |
|---|---|
| Age, Continuous | 57 years |
| Race/Ethnicity, Customized Black, not of hispanic origin | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 107 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants |
| Region of Enrollment United States | 112 Participants |
| Sex: Female, Male Female | 112 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 102 |
| other Total, other adverse events | 57 / 102 |
| serious Total, serious adverse events | 16 / 102 |
Outcome results
Primary
Recurrence-free Survival
Recurrence-free survival curves will be plotted for subjects treated with stage I and II disease.
Time frame: Time from the start of treatment to recurrence, second malignancy, or death as a first event, assessed up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy With or Without Maintenance Therapy) | Recurrence-free Survival | 98 percentage of subjects |