Estrogen Receptor-positive Breast Cancer, HER2-positive Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer
Conditions
Brief summary
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as filgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. 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. Giving combination chemotherapy and filgrastim together with trastuzumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride, cyclophosphamide, and filgrastim together followed by paclitaxel albumin-stabilized nanoparticle formulation and trastuzumab works in treating patients with breast cancer previously treated with surgery
Detailed description
PRIMARY OBJECTIVES: I. To assess disease-free survival following a dose-intensive weekly regimen of Adriamycin + oral cyclophosphamide augmented with G-CSF support followed by Abraxane and Herceptin if appropriate for adjuvant treatment of high risk breast cancer patients. SECONDARY OBJECTIVES: I. To assess the toxicity associated with this regimen. II. To assess the delivered dose intensity of the regimen. III. To assess time to treatment failure and overall survival of the regimen. IV. To assess the incidence and severity of delayed nausea and vomiting with this regimen. OUTLINE: Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
Interventions
DRUGdoxorubicin hydrochloride
Given IV
DRUGcyclophosphamide
Given orally
BIOLOGICALfilgrastim
Given SC
DRUGpaclitaxel albumin-stabilized nanoparticle formulation
Given IV
BIOLOGICALtrastuzumab
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
PROCEDUREquality-of-life assessment
Ancillary studies
Sponsors
University of Washington
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a histologically confirmed diagnosis of primary breast carcinoma that has been surgically resected; (this regimen is not intended for neoadjuvant treatment) * 4 + nodes * OR if 1-3 + nodes, either ER OR HER-2/neu+ * OR have high-risk node negative disease that is HER-2/neu positive OR \>= 2.0 cm tumor size * HER-2/new + definition: patient has known tumor HER-2/new expression = 3+ by IHC or, if 2+ by IHC confirmed to be FISH positive * Patients with clinically apparent cardiac disease, or history of same, are not eligible; patients who are \>= 60 years of age or who have a history of hypertension must have an echocardiogram or MUGA prior to enrollment; patients with breast cancer that is HER-2/neu positive and a treatment plan that includes Herceptin must have an echocardiogram or MUGA scan prior to enrollment; the LVEF must be within the institutional normal range; if LVEF is \> 75%, the investigator should consider having the LVEF reviewed or repeating the MUGA prior to registration * WBC \>= 4,000 * ANC \>= 1,500 * Platelet count \>= 100,000 * Serum creatinine =\< 1.5 x IULN * Bilirubin =\< 2.0 * SGOT/SGPT/alkaline phosphatase =\< 2 x IULN * Elevations greater than these require metastatic work up * Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures
Exclusion criteria
* Except for the following, no other malignancy is allowed: synchronous ipsilateral breast cancer of the same subtype (ER/PR, HER-2/neu), adequately treated basal cell or squamous cell skin cancer, in situcervical cancer or other stage I or II cancer from which the patient has been disease free for at least 5 years * Patients with cardiac disease that would preclude the use of Adriamycin, Taxol or Herceptin are not eligible; this includes: * Angina pectoris that requires the use of antianginal medication * Cardiac arrhythmia requiring medication * Severe conduction abnormality * Clinically significant valvular disease * Cardiomegaly on chest x-ray * Ventricular hypertrophy on EKG * Uncontrolled hypertension, (diastolic greater than 100 mm/Hg or systolic \> 200 mm/hg) * Current use of digitalis or beta blockers for CHF * Clinically significant pericardial effusion * Myocardial infarction documented as a clinical diagnosis or by EKG or any other test * Documented congestive heart failure * Documented cardiomyopathy * Documented arrhythmia or cardiac valvular disease that requires medication or is medically significant * Patients who have received prior chemotherapy or radiotherapy are not eligible * Patients who are pregnant or breastfeeding are not eligible; women of child bearing potential must agree to practice adequate contraception * Patients with active infection are not eligible * Patients who are known to be infected with HIV, hepatitis B or hepatitis C are not eligible; testing is not required unless there is a high index of clinical suspicion * Patients suffering from psychiatric impairment are not eligible
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-free Survival Following a Dose-intensive Weekly Regimen of Adriamycin + Oral Cyclophosphamide Augmented With G-CSF Support Followed by Abraxane and Herceptin | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delivered Dose Intensity of the Regimen | After at least one course of Adriamycin, up to 12 weeks. | — |
| Toxicity Associated With This Regimen | After at least one course of Adriamycin, up to 12 weeks. | — |
| Time to Treatment Failure | Up to 6 years | Median time from date of start of therapy to date of removal from therapy for reason other than completion, date of first observation of recurrent disease or date of death due to any cause whichever comes first. |
| Overall Survival | Up to 6 years. | Count of surviving patients at two years and six years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.
doxorubicin hydrochloride: Given IV
cyclophosphamide: Given orally
filgrastim: Given SC
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
trastuzumab: Given IV
laboratory biomarker analysis: Correlative studies
quality-of-life assessment: Ancillary studies | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Arm I |
|---|---|
| Age, Continuous | 52 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 51 Participants |
| Sex: Female, Male Female | 60 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 | 33 / 60 |
| serious Total, serious adverse events | 5 / 60 |
Outcome results
Primary
Disease-free Survival Following a Dose-intensive Weekly Regimen of Adriamycin + Oral Cyclophosphamide Augmented With G-CSF Support Followed by Abraxane and Herceptin
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I | Disease-free Survival Following a Dose-intensive Weekly Regimen of Adriamycin + Oral Cyclophosphamide Augmented With G-CSF Support Followed by Abraxane and Herceptin | 56 Participants |
Secondary
Delivered Dose Intensity of the Regimen
Time frame: After at least one course of Adriamycin, up to 12 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I | Delivered Dose Intensity of the Regimen | Doxorubicin | 92.6 percentage of mean administered dose |
| Arm I | Delivered Dose Intensity of the Regimen | Cyclophosphamide | 92.1 percentage of mean administered dose |
| Arm I | Delivered Dose Intensity of the Regimen | nP (intent-to-treat) | 88.0 percentage of mean administered dose |
Secondary
Overall Survival
Count of surviving patients at two years and six years
Time frame: Up to 6 years.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I | Overall Survival | Two years | 59 Participants |
| Arm I | Overall Survival | Six years | 53 Participants |
Secondary
Time to Treatment Failure
Median time from date of start of therapy to date of removal from therapy for reason other than completion, date of first observation of recurrent disease or date of death due to any cause whichever comes first.
Time frame: Up to 6 years
Population: Outcome measure reported only for those that had an event (death, recurrent disease or removal).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I | Time to Treatment Failure | 2.7 years |
Secondary
Toxicity Associated With This Regimen
Time frame: After at least one course of Adriamycin, up to 12 weeks.
Population: Some results reported are only considered amongst patients receiving Trastuzumab (n = 15).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I | Toxicity Associated With This Regimen | Filgrastim used | 37 Participants |
| Arm I | Toxicity Associated With This Regimen | Dose holds/reductions | 43 Participants |
| Arm I | Toxicity Associated With This Regimen | Hospitalization/ER evaluation | 5 Participants |
| Arm I | Toxicity Associated With This Regimen | Trastuzumab patients with decease in LVEF to <50% | 2 Participants |
| Arm I | Toxicity Associated With This Regimen | Trastuzumab patients with decease in LVEF to <10% | 3 Participants |