Breast Cancer
Conditions
Keywords
inflammatory breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
RATIONALE: 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. Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving trastuzumab together with docetaxel and carboplatin may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving trastuzumab together with docetaxel and carboplatin works in treating women with stage II, stage III, or inflammatory breast cancer.
Detailed description
OBJECTIVES: Primary * Determine the antitumor activity of trastuzumab (Herceptin\^®), docetaxel, and carboplatin, as measured by tumor response rate, in women with previously untreated HER2/neu-positive stage IIB, IIIA, IIIB, or IIIC or inflammatory breast cancer. Secondary * Determine the pathological complete response in patients treated with this regimen. * Determine the disease-free survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Determine pathologic and molecular markers for predicting efficacy of this regimen in these patients. OUTLINE: This is a non-randomized, multicenter study. * Course 1 (days 1-28): Patients receive trastuzumab (Herceptin\^®) IV over 30-90 minutes on days 1, 8, 15, and 22 and docetaxel IV over 1 hour and carboplatin IV over 30-60 minutes on day 8. * Course 2-6: Patients receive trastuzumab IV over 30 minutes on days 1, 8, and 15 during courses 2-5 and on days 1, 8, 15, and 22 during course 6. Patients also receive docetaxel IV over 1 hour and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 5 additional courses (6 courses total) in the absence of disease progression or unacceptable toxicity. Three weeks after completion of course 6, patients undergo restaging. Patients with local operable disease undergo modified radical mastectomy or lumpectomy and axillary node dissection followed by radiotherapy. Patients also receive trastuzumab IV once every 3 weeks for up to 52 weeks of total treatment (including the 6 courses of trastuzumab, docetaxel, and carboplatin) in the absence of disease progression or unacceptable toxicity. Patients who do not have local operable disease continue to receive trastuzumab as above. PROJECTED ACCRUAL: A total of 13-43 patients will be accrued for this study.
Interventions
BIOLOGICALherceptin
DRUGcarboplatin
DRUGdocetaxel
PROCEDUREconventional surgery
Modified radical mastectomy or lumpectomy and axillary node dissection
PROCEDUREradiation therapy
Whole breast or chest wall irradiation (as determined by radiologist)
Sponsors
National Cancer Institute (NCI)
Aventis Pharmaceuticals
University of Medicine and Dentistry of New Jersey
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
DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer, meeting 1 of the following stage criteria: * Stage IIB (T3, N0) * Stage IIIA (N0-N2) * Stage IIIB (T4, N0-2) * Stage IIIC * Inflammatory breast cancer * HER2/neu-positive disease by fluorescence in situ hybridization * Biopsy-accessible tumor * Measurable disease by physical examination or x-ray * No stage IV disease * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 and over Sex * Female Menopausal status * Not specified Performance status * ECOG 0-2 Life expectancy * At least 8 weeks Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Meets 1 of the following criteria: * SGOT and SGPT ≤ 5 times upper limit of normal (ULN) AND alkaline phosphatase normal * SGOT and SGPT ≤ 1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN * SGOT and SGPT normal AND alkaline phosphatase ≤ 5 times ULN * Bilirubin normal Renal * Creatinine normal * No pre-existing clinically significant renal disease that is not related to the malignancy Cardiovascular * Ejection fraction ≥ 50% by MUGA * No pre-existing clinically significant cardiac disease that is not related to the malignancy * No history of congestive heart failure Pulmonary * No pre-existing clinically significant pulmonary disease that is not related to the malignancy Gastrointestinal * No severe malnutrition * No intractable emesis Neurologic * No pre-existing clinically significant neurologic disease that is not related to the malignancy * No peripheral neuropathy ≥ grade 2 * No nerve damage from diabetes Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective non-hormonal contraception during and for 4 weeks after completion of study treatment * No known allergic reaction to study drugs * No active infection * No other malignancy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No other pre-existing clinically significant disease that is not related to the malignancy * No other serious or significant medical condition that would preclude study participation * No other contraindication to study treatment PRIOR CONCURRENT THERAPY: Biologic therapy * No other concurrent immunotherapy Chemotherapy * No prior chemotherapy for the malignancy * No other concurrent chemotherapy Endocrine therapy * No concurrent hormonal therapy for the malignancy Radiotherapy * No concurrent radiotherapy Surgery * No concurrent surgery for the malignancy Other * More than 2 weeks since prior and no concurrent herbal remedies or aspirin-containing products * No other concurrent investigational or commercial agents or therapies for the malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Antitumor Activity as Measured by Response Rate | 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Pathological Complete Response | 5 years |
| Disease-free Survival | 10 years |
| Pathologic and Molecular Markers for Predicting Efficacy | 5 years |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Cancer Institute of New Jersey (a comprehensive cancer center) and 3 community hospitals within NJ from March 2005 through January 2007.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel, Carboplatin and Trastuzumab A total of six cycles of TCH \[(Taxotere® (75 mg/m2) + Carboplatin (AUC = 6) + Herceptin® (2 mg/kg weekly after a 4 mg/kg load on Day 1)\] will be administered every 3 weeks.Three weeks after receiving the sixth cycle of TCH, all patients will be restaged.
* Those determined to have localized and operable disease will undergo a modified radical mastectomy or lumpectomy and axillary node dissection. After recovery from surgery, the patients will receive whole breast or chest wall irradiation (as determined by radiologist) with concurrent Herceptin® (6 mg/kg). Following radiation, patients will continue Herceptin® (6 mg/kg) every 3 weeks until they have been on study for a total of 52 weeks.
* If patients are staged and are negative they will continue Herceptin® (6 mg/kg)every 3 weeks until they have been on study for a total of 52 weeks. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Docetaxel, Carboplatin and Trastuzumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age Continuous | 46.4 years STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 5 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 | 4 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Antitumor Activity as Measured by Response Rate
Time frame: 5 years
Population: Study was terminated early and insufficient data were collected to evaluate this outcome measure.
Secondary
Disease-free Survival
Time frame: 10 years
Population: Study was terminated early and insufficient data were collected to evaluate this outcome measure.
Secondary
Pathological Complete Response
Time frame: 5 years
Population: Study was terminated early and insufficient data were collected to evaluate this outcome measure.
Secondary
Pathologic and Molecular Markers for Predicting Efficacy
Time frame: 5 years
Population: Study was terminated early and insufficient data were collected to evaluate this outcome measure.