Trastuzumab, Docetaxel, and Carboplatin in Treating Women With Stage II, Stage III, or Inflammatory Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Trial of Taxotere, Carboplatin and Herceptin in Locally Advanced or Inflammatory Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: herceptin
* Drug: carboplatin
* Drug: docetaxel
* Procedure: conventional surgery
* Procedure: radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel, Carboplatin and Trastuzumab<br>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 (as determined by surgical consultation) 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. | Biological: herceptin<br> <br> * Other names: trastuzumb;Drug: carboplatin<br> <br> Drug: docetaxel<br> <br> * Other names: Taxotere;Procedure: conventional surgery<br>* Modified radical mastectomy or lumpectomy and axillary node dissection<br>Procedure: radiation therapy<br>* Whole breast or chest wall irradiation (as determined by radiologist)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor Activity as Measured by Response Rate |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response |  | 5 years | 
| Disease-free Survival |  | 10 years | 
| Pathologic and Molecular Markers for Predicting Efficacy |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammatory breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer