Docetaxel, Doxorubicin, and Cyclophosphamide in Treating Women With Advanced Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, doxorubicin, and cyclophosphamide, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them at different times, may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for breast cancer. PURPOSE: Randomized phase I trial to compare the effectiveness of two regimens of docetaxel combined with doxorubicin and cyclophosphamide in treating women who have advanced breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the pharmacokinetic profile of docetaxel, doxorubicin, and cyclophosphamide in women with advanced breast cancer. Secondary Compare the pharmacokinetic profile of this regimen in these patients vs the historical pharmacokinetic profile of docetaxel. OUTLINE: This is a randomized, open-label, crossover, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive doxorubicin IV over 15 minutes and cyclophosphamide IV over 15 minutes on day 1 followed by doxorubicin IV over 15 minutes, cyclophosphamide IV over 15 minutes, and docetaxel IV over 1 hour on day 22. Arm II: Patients receive doxorubicin IV over 15 minutes, cyclophosphamide IV over 15 minutes, and docetaxel IV over 1 hour on day 1 followed by doxorubicin IV over 15 minutes and cyclophosphamide IV over 15 minutes on day 22. Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. Patients may receive additional therapy at the discretion of the treating physician. Patients are followed at 3-4 weeks. PROJECTED ACCRUAL: A total of 24 patients (12 per treatment arm) will be accrued for this study within 7 months.

Official Title
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A Pharmacokinetic Interaction Study Of Docetaxel (Taxotere) 75 mg/mIV On The Combination Therapy Doxorubicin (50 mg/m) And Cyclophosphamide (50 mg/m) In The Treatment Of Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: docetaxel
* Drug: doxorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced breast cancer Adjuvant setting for high-risk disease allowed No symptomatic evidence or history of brain metastases No leptomeningeal metastases Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 to 69 Sex Female Menopausal status Not specified Performance status WHO 0-2 OR Karnofsky 60-100% Life expectancy Not specified Hematopoietic Neutrophil count at least 2,000/mm^3 Platelet count greater than 100,000/mm^3 Hemoglobin greater than 10 g/dL Hepatic Bilirubin less than upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN (1.5 times ULN if alkaline phosphatase greater than 2.5 times ULN) Alkaline phosphatase no greater than 5 times ULN Renal Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular LVEF or shortening fraction greater than lower limit of normal by MUGA or echocardiography Cardiac function normal No congestive heart failure No unstable angina pectoris No myocardial infarction within the past year No uncontrolled hypertension No high-risk uncontrolled arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception No active uncontrolled infection No active peptic ulcer No unstable diabetes mellitus No other serious illness or medical condition No contraindication to corticosteroids No pre-existing grade 2 or greater motor or sensory neurotoxicity No psychological, social, familial, or geographical reason that would preclude study follow-up No history of significant neurologic or psychiatric disorder (e.g., psychotic disorder, dementia, or seizures) that would preclude understanding and giving informed consent No other neoplasm within the past 10 years except curatively treated nonmelanoma skin cancer, carcinoma in situ of the cervix, ipsilateral ductal carcinoma in situ of the breast, or lobular carcinoma in situ of the breast PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 6 months since prior anthracycline or taxoid (e.g., paclitaxel or docetaxel) therapy No prior cumulative anthracycline dose greater than 240 mg/m^2 Endocrine therapy Concurrent corticosteroid treatment allowed provided treatment was initiated more than 6 months before study entry and at a dose of less than 20 mg of methylprednisolone or equivalent No concurrent ovarian hormonal replacement therapy Radiotherapy Not specified Surgery More than 2 weeks since prior major surgery Other More than 30 days since prior participation in another clinical trial with any investigational drug or device No other concurrent experimental drugs No other concurrent systemic anticancer therapy No concurrent aminoglycoside antibiotics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cyclophosphamide|nan|
|Drug: docetaxel|nan|
|Drug: doxorubicin hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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