Combination Chemotherapy Plus Biological Therapy in Treating Patients With Stage II or Stage III Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. Combining chemotherapy with biological therapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects of giving chemotherapy together with biological therapy and to see how well they work in treating patients with stage II or stage III breast cancer.

Detailed Description
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OBJECTIVES: Determine the toxic effects of sequential paclitaxel (or other taxane), doxorubicin, and cyclophosphamide followed by immunotherapy with activated T cells, interleukin-2, and sargramostim (GM-CSF) in patients with high-risk stage II or III breast cancer. Determine the disease-free survival and overall survival of patients treated with this regimen. Determine the immune function of patients treated with this regimen. OUTLINE: Patients are stratified according to number of positive lymph nodes (less than 4 nodes vs 4-9 nodes vs 10 or more nodes), type of taxane chemotherapy during study (paclitaxel vs other taxane), and prior treatment with 2 of 3 study chemotherapy agents (yes vs no). Patients receive doxorubicin IV on day 1 and filgrastim (G-CSF) on days 3-10 of 3 consecutive 14-day courses. Patients then receive paclitaxel or another taxane IV on day 1 and G-CSF on days 3-10 of 3 consecutive 14-day courses. Patients then receive cyclophosphamide IV on day 1 and G-CSF on days 3-10 of 3 consecutive 14-day courses. Patients who enroll after previously receiving 2 of these 3 chemotherapy drugs may receive the third. Treatment continues in the absence of disease progression or unacceptable toxicity. After recovery from chemotherapy, patients undergo peripheral blood mononuclear cell (PBMC) collection. The PBMC are treated ex vivo with monoclonal antibody OKT3 to form activated T cells (ATC). The ATC are expanded for up to 14 days in interleukin-2 (IL-2). At 3-4 weeks after PBMC collection, patients receive ATC IV over 15-30 minutes weekly for 8 weeks. Patients also receive IL-2 subcutaneously (SC) daily and sargramostim (GM-CSF) SC twice weekly beginning 3 days before the first ATC infusion and continuing until 7 days after completion of ATC therapy. Patients are followed every 3 months for 1 year and then annually thereafter. PROJECTED ACCRUAL: A total of 40-60 patients will be accrued for this study within 4-5 years.

Official Title
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Combination of Chemotherapy With Taxol, Adriamycin, and Cytoxan (TAC), Multiple Infusions of Activated T Cells (ATC), Interleukin-2 (IL-2) and GM-CSF for High Risk Breast Cancer With and Without Her2/Neu Overexpression. (Phase I/II)

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: aldesleukin
* Biological: filgrastim
* Biological: sargramostim
* Biological: therapeutic autologous lymphocytes
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage II or III adenocarcinoma of the breast High-risk disease At least 4 positive lymph nodes Fewer than 4 positive lymph nodes considered high-risk if one of the following is present: HER2/neu-positive disease Enlarged axillary nodes Extra capsular extension of tumor from lymph node Dermal lymphatic invasion Vascular invasion Bilateral disease Familial breast cancer T4 locally advanced disease Clinically chemosensitive to prior paclitaxel (or other taxane), doxorubicin, and cyclophosphamide No relapse after chemotherapy No clinical evidence of brain metastases Hormone receptor status: Estrogen and progesterone receptor status known PATIENT CHARACTERISTICS: Age: 18 and over Sex: Female Menopausal status: Not specified Performance status: Karnofsky 70-100% OR ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: Granulocyte count at least 1,500/mm^3 Platelet count at least 50,000/mm^3 Hemoglobin greater than 8 g/dL Hepatic: Bilirubin less than 1.5 times normal SGOT less than 1.5 times normal Renal Creatinine less than 1.8 mg/dL Creatinine clearance at least 60 mL/min BUN less than 1.5 times normal Cardiovascular: Ejection fraction at least 45% by MUGA No uncontrolled or significant cardiovascular disease No myocardial infarction within the past year No significant congestive heart failure Pulmonary: FEV_1 at least 60% predicted DLCO at least 60% predicted FVC at least 60% predicted Other: No other malignancy except curatively treated squamous cell carcinoma in situ of the cervix or basal cell skin cancer No other serious medical or psychiatric illness that would preclude study participation HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Prior standard chemotherapy with anthracyclines or combination chemotherapy involving a combination of taxanes, doxorubicin, and/or cyclophosphamide allowed Endocrine therapy: No concurrent hormonal therapy for breast cancer Concurrent hormonal therapy for nondisease-related conditions (e.g., insulin for diabetes) allowed Concurrent steroids for adrenal failure, septic shock, or pulmonary toxicity allowed Radiotherapy: Not specified Surgery: Prior complete resection of tumor allowed Other: Prior successful neoadjuvant therapy allowed

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

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: filgrastim|nan|
|Biological: sargramostim|nan|
|Biological: therapeutic autologous lymphocytes|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: paclitaxel|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  |  | 
| Disease-free survival |  |  | 
| Overall survival |  |  | 
| Immune functions |  |  | 

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