Breast Cancer
Conditions
Keywords
stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage II breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether docetaxel and carboplatin are more effective with or without trastuzumab in treating breast cancer. PURPOSE: This randomized phase II trial is studying how well giving docetaxel together with carboplatin and trastuzumab before surgery works compared to docetaxel and carboplatin alone before surgery in treating women with locally advanced breast cancer.
Interventions
BIOLOGICALtrastuzumab
Cycle 5-7 post-op only Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 8 Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV
DRUGcarboplatin
Cycle 1-8 Day 1 or 2 AUC = 6 IV
DRUGdocetaxel
Cycle 1-8 Day 1 or 2: 75 mg/m2 IV
Sponsors
Aventis Pharmaceuticals
Genentech, Inc.
Jonsson Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed infiltrating adenocarcinoma of the breast * Primary breast cancer \> 5cm, or skin/chest wall involvement, any N, without evidence of metastasis. * No prior radiation to the involved breast * ECOG (Electrocochleography) performance status 0-2 * Age 18 years to 80 years * Absolute Neutrophil count \> 1500 cell/μl, platelet count \> 100000 cells/μl and hemoglobin \> 9 g/dl * All liver function tests \< upper limit of normal * Serum creatinine \< 2.0 mg/dl * Normal left ventricular ejection fraction (LVEF) as determined by MUGA (Multiple Gated Acquisition) scan or echocardiogram * HER-2/neu status is determined by a FISH (Fluorescence in situ hybridization) test. \[FISH (+) is HER-2/neu (+)\] * If female of childbearing potential, pregnancy test is negative * If premenopausal and not surgically sterilized, the patient agrees to use effective birth control method for the duration of the study * Informed consent has been obtained
Exclusion criteria
* Non-confirmed infiltrating adenocarcinoma breast cancer * Evidence of metastasis * Previous chemotherapy using the drugs proposed in this study, specifically Herceptin®, Taxotere®, and/or Carboplatin * Prior radiation to the involved breast * Recent breast cancer drug therapy within last 5 years of any form * History of allergy to polysorbate or castor oil * Ongoing active infection * Concurrent life-limiting disease with a life expectancy of less than one year * Past or current history of other malignancy within the past 5 years which could affect the diagnosis or assessment of breast cancer, except for curatively treated non-melanoma skin cancer and/or in situ carcinoma of the cervix * Pregnancy, nursing, fertile women who do not use birth control device * Inability to give informed consent * Patients with pre-existing peripheral neuropathy \> grade 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | 5 years | Objective response rate of patients treated with Taxotere/carboplatin with or without Herceptin preoperatively. Objective response equals the combination of complete response (CR), partial response (PR) and marginal response (MR). Tumor size was assessed by (1) physical examination, (2) mammography and (3) MRI. 5 response groups: complete response (CR), partial response (PR), marginal response (MR), stable disease (SD) & disease progression (DP). Pathologic response assigned into 2 groups: pCR and non-pCR. pCR-no evidence of residual invasive disease in specimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Tumor Response by Physical Exam and Imaging Studies | 5 years | — |
| Tumor Response Assessment | 5 years | Measured by physical examination compared to breast mammography and MRI assessment |
| Clinico-histologic Predictors of pCR (Pathologic Complete Response) | 5 years | — |
| Pathologic Nodal Status | 5 years | According to Primary Tumor Response Pathologic lymph node status N0 Axillary and other nearby lymph nodes do not have cancer (when looked at under a microscope) N1 Micrometastases (very small clusters of cancer) OR 1-3 axillary lymph nodes have cancer AND/OR Internal mammary nodes have tiny amounts of cancer found on sentinel node biopsy N2 4-9 axillary lymph nodes have cancer OR Internal mammary nodes have cancer, but axillary lymph nodes do not have cancer N3 10 or more axillary lymph nodes have cancer OR Infraclavicular (under the clavicle) nodes have cancer OR Internal mammary nodes have cancer plus 1 or more axillary lymph nodes have cancer OR 4 or more axillary lymph nodes have cancer plus internal mammary nodes have cancer or micrometastases found on sentinel node biopsy OR Supraclavicular (above the clavicle) nodes have cancer |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment period: 2002-2007 Types of location: oncology outpatient clinics
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Neoadjuvant Therapy) see intervention description
carboplatin: Cycle 1-8 Day 1 or 2 AUC = 6 IV
docetaxel: Cycle 1-8 Day 1 or 2: 75 mg/m2 IV
trastuzumab: Cycle 1-4 pre-op Day 1 4mg/kg IV Day 8, 15 2mg/kg IV
Cycle 5-7 post-op Day 1 4mg/kg IV Day 8, 15 2mg/kg IV
Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV | 15 |
| Arm II (Neoadjuvant Therapy) please see intervention description
trastuzumab: Cycle 5-7 post-op only Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 8 Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV
carboplatin: Cycle 1-8 Day 1 or 2 AUC = 6 IV
docetaxel: Cycle 1-8 Day 1 or 2: 75 mg/m2 IV | 15 |
| HER2/Neu Negative Patients please see intervention description
carboplatin: Cycle 1-8 Day 1 or 2 AUC = 6 IV
docetaxel: Cycle 1-8 Day 1 or 2: 75 mg/m2 IV | 44 |
| Total | 74 |
Baseline characteristics
| Characteristic | Arm I (Neoadjuvant Therapy) | Arm II (Neoadjuvant Therapy) | HER2/Neu Negative Patients | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 44 Participants | 74 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 44 participants | 74 participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 44 Participants | 74 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 | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 15 | 4 / 14 | 10 / 45 | 20 / 74 |
| other Total, other adverse events | 15 / 15 | 12 / 14 | 45 / 45 | 72 / 74 |
| serious Total, serious adverse events | 6 / 15 | 4 / 14 | 10 / 45 | 20 / 74 |
Outcome results
Primary
Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively.
Objective response rate of patients treated with Taxotere/carboplatin with or without Herceptin preoperatively. Objective response equals the combination of complete response (CR), partial response (PR) and marginal response (MR). Tumor size was assessed by (1) physical examination, (2) mammography and (3) MRI. 5 response groups: complete response (CR), partial response (PR), marginal response (MR), stable disease (SD) & disease progression (DP). Pathologic response assigned into 2 groups: pCR and non-pCR. pCR-no evidence of residual invasive disease in specimen.
Time frame: 5 years
Population: pCR was not assessed for 2 patients in the HER2 - (Pre-Op TC) group \[1 protocol violation, 1 bilateral disease\] and for 1 patient in the HER2+ (Pre-Op TC, Post-Op Herceptin) group \[protocol violation\]
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: HER2+ | Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | DFS (Disease Free Survival) | 13 participants |
| Arm I: HER2+ | Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | OS (overall survival) | 13 participants |
| Arm II: HER2+ | Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | OS (overall survival) | 11 participants |
| Arm II: HER2+ | Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | DFS (Disease Free Survival) | 8 participants |
| HER2- | Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | DFS (Disease Free Survival) | 33 participants |
| HER2- | Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | OS (overall survival) | 39 participants |
| Total | Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | DFS (Disease Free Survival) | 54 participants |
| Total | Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | OS (overall survival) | 63 participants |
Secondary
Clinical Tumor Response by Physical Exam and Imaging Studies
Time frame: 5 years
Population: Clinical response was not assessed for 2 patients in the HER2 - (Pre-Op TC) group \[1 protocol violation, 1 bilateral disease\] and for 1 patient in the HER2+ (Pre-Op TC, Post-Op Herceptin) group \[protocol violation\]
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: HER2+ | Clinical Tumor Response by Physical Exam and Imaging Studies | Partial Response | 7 participants |
| Arm I: HER2+ | Clinical Tumor Response by Physical Exam and Imaging Studies | Complete Response | 8 participants |
| Arm I: HER2+ | Clinical Tumor Response by Physical Exam and Imaging Studies | Marginal Response | 0 participants |
| Arm II: HER2+ | Clinical Tumor Response by Physical Exam and Imaging Studies | Partial Response | 7 participants |
| Arm II: HER2+ | Clinical Tumor Response by Physical Exam and Imaging Studies | Complete Response | 5 participants |
| Arm II: HER2+ | Clinical Tumor Response by Physical Exam and Imaging Studies | Marginal Response | 1 participants |
| HER2- | Clinical Tumor Response by Physical Exam and Imaging Studies | Complete Response | 18 participants |
| HER2- | Clinical Tumor Response by Physical Exam and Imaging Studies | Marginal Response | 4 participants |
| HER2- | Clinical Tumor Response by Physical Exam and Imaging Studies | Partial Response | 21 participants |
Secondary
Clinico-histologic Predictors of pCR (Pathologic Complete Response)
Time frame: 5 years
Population: ER (estrogen-receptor), PR (progesterone-receptor), HER2 (human epidermal growth factor receptor 2), FISH (Fluorescence in situ hybridization), IDC (invasive ductal carcinoma), ILC (invasive lobular carcinoma),
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | T-Stage T2 | 5 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER and PR both negative | 9 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | T-Stage T4 | 1 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER-negative | 11 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Tumor Type - IDC only | 19 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER and PR one negative | 7 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Tumor Type - all others (compared to IDC only) | 0 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | PR-negative | 14 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Tumor Type - ILC only | 0 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER and PR both positive | 3 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Tumor Type - all other comparted to (ICL only) | 19 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | T-Stage T3 | 13 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Triple Negative-yes | 6 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | HER2 negative | 12 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Triple Negative-no | 7 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | PR-positive | 5 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | FISH positive Herceptin No | 1 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | HER2 positive | 7 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | FISH positive Herceptin Yes | 6 participants |
| Arm I: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER-positive | 8 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | FISH positive Herceptin Yes | 9 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER-negative | 14 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER-positive | 38 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | PR-negative | 24 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | PR-positive | 28 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER and PR both negative | 14 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER and PR one negative | 10 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | ER and PR both positive | 28 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | HER2 negative | 30 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | HER2 positive | 22 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | T-Stage T3 | 27 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | T-Stage T4 | 16 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Tumor Type - IDC only | 38 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Tumor Type - all others (compared to IDC only) | 14 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Tumor Type - ILC only | 9 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Tumor Type - all other comparted to (ICL only) | 43 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Triple Negative-yes | 5 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | Triple Negative-no | 38 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | FISH positive Herceptin No | 13 participants |
| Arm II: HER2+ | Clinico-histologic Predictors of pCR (Pathologic Complete Response) | T-Stage T2 | 9 participants |
Secondary
Pathologic Nodal Status
According to Primary Tumor Response Pathologic lymph node status N0 Axillary and other nearby lymph nodes do not have cancer (when looked at under a microscope) N1 Micrometastases (very small clusters of cancer) OR 1-3 axillary lymph nodes have cancer AND/OR Internal mammary nodes have tiny amounts of cancer found on sentinel node biopsy N2 4-9 axillary lymph nodes have cancer OR Internal mammary nodes have cancer, but axillary lymph nodes do not have cancer N3 10 or more axillary lymph nodes have cancer OR Infraclavicular (under the clavicle) nodes have cancer OR Internal mammary nodes have cancer plus 1 or more axillary lymph nodes have cancer OR 4 or more axillary lymph nodes have cancer plus internal mammary nodes have cancer or micrometastases found on sentinel node biopsy OR Supraclavicular (above the clavicle) nodes have cancer
Time frame: 5 years
Population: only 71 subjects of the 74 subjects could be analyzed for this outcome measure due to data collection error.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: HER2+ | Pathologic Nodal Status | N(0) | 9 participants |
| Arm I: HER2+ | Pathologic Nodal Status | N+ | 6 participants |
| Arm II: HER2+ | Pathologic Nodal Status | N(0) | 4 participants |
| Arm II: HER2+ | Pathologic Nodal Status | N+ | 11 participants |
| HER2- | Pathologic Nodal Status | N(0) | 21 participants |
| HER2- | Pathologic Nodal Status | N+ | 23 participants |
Secondary
Tumor Response Assessment
Measured by physical examination compared to breast mammography and MRI assessment
Time frame: 5 years
Population: pCR was not assessed for 2 patients in the HER2 - (Pre-Op TC) group \[1 protocol violation, 1 bilateral disease\] and for~1 patient in the HER2+ (Pre-Op TC, Post-Op Herceptin) group \[protocol violation\]
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: HER2+ | Tumor Response Assessment | 6 participants |
| Arm II: HER2+ | Tumor Response Assessment | 1 participants |
| HER2- | Tumor Response Assessment | 12 participants |