Breast Cancer
Conditions
Keywords
inflammatory breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer, Paget disease of the breast with invasive ductal carcinoma, invasive ductal breast carcinoma with predominant intraductal component, invasive ductal breast carcinoma, medullary ductal breast carcinoma with lymphocytic infiltrate, comedo ductal breast carcinoma, invasive lobular breast carcinoma with predominant in situ component, invasive lobular breast carcinoma, mucinous ductal breast carcinoma, papillary ductal breast carcinoma, tubular 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. 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 with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer. PURPOSE: This randomized phase II trial is comparing two different regimens of combination chemotherapy given together with or without trastuzumab to see how well they work in treating patients with stage II or stage III breast cancer.
Detailed description
OBJECTIVES: Primary * Compare 2 neoadjuvant chemotherapy regimens (docetaxel, doxorubicin hydrochloride, and cyclophosphamide \[TAC\] vs doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin \[ACAC\]), in terms of toxicities and effectiveness as defined by the pathological complete remission rate, in patients with non HER2/neu overexpressing stage II or III breast cancer. * Evaluate the probability of achieving a pathological complete remission when adding trastuzumab (Herceptin®) to ACAC in the subset of patients with HER2/neu overexpressing stage II or III breast cancer. Secondary * Identify prognostic and predictive markers of outcome, recurrence, and targets of therapy. OUTLINE: This is a randomized study. Patients with non HER2/neu overexpressing tumors are randomized to 1 of 2 treatment arms. Patients with HER2/neu overexpressing tumors are assigned to arm III. * Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses. * Arm II: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and paclitaxel repeats every 4 weeks for 3 courses. * Arm III: Patients receive chemotherapy as in arm II. They also receive trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin. Within 4 weeks after completion of chemotherapy with or without trastuzumab (Herceptin®), all patients undergo surgery. PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.
Interventions
DRUGcyclophosphamide
Given IV
DRUGdocetaxel
Given IV
DRUGdoxorubicin hydrochloride
Given IV
BIOLOGICALTrastuzumab
Given IV
DRUGCarboplatin
Given IV
DRUGPaclitaxel
Given IV
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
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically proven infiltrating ductal or lobular breast carcinoma * Stage II or III disease * Inflammatory breast cancer allowed * Hormone-receptor status not specified PATIENT CHARACTERISTICS: * ECOG performance status \< 2 * Male or female * Menopausal status not specified (for female patients) * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Bilirubin normal (except for patient's with Gilbert's disease) * Creatinine ≤ 1.2 mg/dL * Creatinine clearance ≥ 70 mL/min * Ejection fraction ≥ 50% on MUGA * No neuropathy ≥ grade 1 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective nonhormonal contraception * No prior malignant disease within the past 5 years, excluding: * Squamous cell or basal cell skin carcinoma * Stage I or in situ cervical carcinoma * No noninvasive (in situ) breast carcinoma within the past 5 years PRIOR CONCURRENT THERAPY: * At least 5 years since prior antiestrogen treatment for any indication other than breast cancer prevention (tamoxifen, raloxifene, or an aromatase inhibitor) * No prior radiotherapy to the chest wall
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Patients With Pathologic Complete Response (pCR) | At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months | pCR was defined as no evidence of residual invasive cancer (or very few scattered tumor cells) in primary tumor and lymph nodes. |
| Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1. | At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months. | RCB score is determined using information on the size of the tumor and the extent of tumor cells in the breast and axillary lymph nodes after neoadjuvant therapy. The higher the RCB score, the more residual breast cancer there is in the breast and lymph nodes: RCB-0 = No residual breast cancer RCB-I = Small amount of residual breast cancer RCB-II = Moderate amount of residual breast cancer RCB-III = Extensive (a lot of) residual breast cancer |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide Patients receive 50 mg/m2 doxorubicin hydrochloride IV, 500 mg/m2 cyclophosphamide IV, and 75 mg/m2 docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses. | 37 |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin Patients receive 60 mg/m2 doxorubicin hydrochloride IV and 600 mg/m2 cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive AUC 2 carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and 100 mg/m2 paclitaxel repeats every 4 weeks for 3 courses. | 40 |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and Trastuzumab Patients receive chemotherapy as in arm II. They also receive 2 mg/kg trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin. | 44 |
| Total | 121 |
Baseline characteristics
| Characteristic | Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide | Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin | Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and Trastuzumab | Total |
|---|---|---|---|---|
| Age, Continuous | 50 years | 49 years | 52 years | 50 years |
| Race/Ethnicity, Customized African American | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized American Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 10 Participants | 13 Participants |
| Race/Ethnicity, Customized Hispanic | 14 Participants | 19 Participants | 12 Participants | 45 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 17 Participants | 19 Participants | 55 Participants |
| Region of Enrollment United States | 37 participants | 40 participants | 44 participants | 121 participants |
| Sex: Female, Male Female | 37 Participants | 40 Participants | 44 Participants | 121 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 37 | 4 / 40 | 4 / 44 |
| other Total, other adverse events | 37 / 37 | 40 / 40 | 44 / 44 |
| serious Total, serious adverse events | 8 / 37 | 5 / 40 | 8 / 44 |
Outcome results
Primary
Count of Patients With Pathologic Complete Response (pCR)
pCR was defined as no evidence of residual invasive cancer (or very few scattered tumor cells) in primary tumor and lymph nodes.
Time frame: At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide | Count of Patients With Pathologic Complete Response (pCR) | 6 Participants |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin | Count of Patients With Pathologic Complete Response (pCR) | 4 Participants |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and Trastuzumab | Count of Patients With Pathologic Complete Response (pCR) | 22 Participants |
Primary
Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1.
RCB score is determined using information on the size of the tumor and the extent of tumor cells in the breast and axillary lymph nodes after neoadjuvant therapy. The higher the RCB score, the more residual breast cancer there is in the breast and lymph nodes: RCB-0 = No residual breast cancer RCB-I = Small amount of residual breast cancer RCB-II = Moderate amount of residual breast cancer RCB-III = Extensive (a lot of) residual breast cancer
Time frame: At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide | Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1. | 11 Participants |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin | Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1. | 10 Participants |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and Trastuzumab | Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1. | 28 Participants |