Dose-Dense Docetaxel Before or After Doxorubicin/Cyclophosphamide in Axillary Node-Positive Breast Cancer

Study Overview
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Brief Summary
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This study will determine if docetaxel will be administered before or after doxorubicin/cyclophosphamides in an adjuvant chemotherapy regimen to be evaluated in a subsequent phase III trial.

Detailed Description
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Rationale: Studies suggest that chemotherapy agents docetaxel, doxorubicin, and cyclophosphamide have some efficacy against different types of breast cancer. However, the optimal sequence in which to administer these treatments remains unknown. The current study assesses two separate sequences of docetaxel, doxorubicin, and cyclophosphamide. Purpose: This study will evaluate two different combination chemotherapy schedules for patients with axillary node-positive breast cancer. Combination one is docetaxel before doxorubicin and cyclophosphamide. Combination two is docetaxel after doxorubicin and cyclophosphamide. The combination with no dose reductions of docetaxel within 10 weeks will then be tested in a Phase III study. The toxicities of docetaxel will also be assessed in study participants. Treatment: Patients in this study will receive one of two chemotherapy combination schedules. A computer will randomly assign patients into their treatment group. Group one will receive docetaxel before doxorubicin and cyclophosphamide. Group two will receive docetaxel after doxorubicin and cyclophosphamide. Patients in group one will receive docetaxel every two weeks for a total of eight weeks. These patients will then be given combination doxorubicin and cyclophosphamide every two weeks for a total of eight weeks. Patients in group two will receive combination doxorubicin and cyclophosphamide every two weeks for a total of eight weeks. These patients will then be given docetaxel every two weeks for a total of eight weeks. Several tests and exams will be given throughout the study to closely monitor patients. Treatments will be discontinued due to disease growth or unacceptable side effects.

Official Title
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Phase II Randomized Adjuvant Trial of Dose-Dense Docetaxel Before or After Doxorubicin/Cyclophosphamide (AC) in Axillary Node-Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Doxorubicin
* Drug: Cyclophosphamide (AC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have histologically or cytologically confirmed breast cancer No metastatic disease Prior lumpectomy or mastectomy No prior chemotherapy or hormone treatments for breast cancer Must have normal organ and marrow function. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Exclusion Criteria: Peripheral neuropathy of grade II or higher. History or evidence upon physical exam of CNS (central nervous system Diseases)disease. History of unstable angina or myocardial infarction within the last six months. Pregnant or nursing women. Known allergies to polysorbate 80. HIV-positive patients.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A (Docetaxel before doxorubicin/cyclophosphamide)<br>Docetaxel 75 mg/m2 every 2 weeks for 4 cycles followed by A (doxorubicin) 60 mg/m2 & C (cyclophosphamide) 600 mg/m2 every 2 weeks for 4 cycles. | Drug: Docetaxel<br>* Arm A:75 mg/m2 every 2 weeks)for 4 cycles. Arm B:75 mg/m2 every 2 weeks for 4 cycles.<br>* Other names: Taxotere;Drug: Doxorubicin<br>* 60 mg/m2 intravenously as push over 2-5 minutes, every 14 days for 4 cycles. Arms: Arm A (Docetaxel before doxorubicin/cyclophosphamide) , Arm B (Docetaxel after doxorubicin/cyclophosphamide)<br>* Other names: hydroxydaunorubicin;Drug: Cyclophosphamide (AC)<br>* 600 mg/m2 over 30 to 60 minutes every 14 days (2 weeks) for 4 cycles. Arms: Arm A (Docetaxel before doxorubicin/cyclophosphamide), Arm B (Docetaxel after doxorubicin/cyclophosphamide)<br>* Other names: CYT;|
| Active Comparator: Arm B (Docetaxel after doxorubicin/cyclophosphamide)<br>A (doxorubicin) 60 mg/m2 & C (cyclophosphamide) 600 mg/m2 every 2 weeks for 4 cycles followed by Docetaxel 75 mg/m2 every 2 weeks for 4 cycles. | Drug: Docetaxel<br>* Arm A:75 mg/m2 every 2 weeks)for 4 cycles. Arm B:75 mg/m2 every 2 weeks for 4 cycles.<br>* Other names: Taxotere;Drug: Doxorubicin<br>* 60 mg/m2 intravenously as push over 2-5 minutes, every 14 days for 4 cycles. Arms: Arm A (Docetaxel before doxorubicin/cyclophosphamide) , Arm B (Docetaxel after doxorubicin/cyclophosphamide)<br>* Other names: hydroxydaunorubicin;Drug: Cyclophosphamide (AC)<br>* 600 mg/m2 over 30 to 60 minutes every 14 days (2 weeks) for 4 cycles. Arms: Arm A (Docetaxel before doxorubicin/cyclophosphamide), Arm B (Docetaxel after doxorubicin/cyclophosphamide)<br>* Other names: CYT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Select one of two adjuvant chemotherapy regimens for evaluation in subsequent phase III trial. | Docetaxel before doxorubicin/cyclophosphamide(AC)or Docetaxel after AC. The regimen selection will be based on the proportion of patients receiving four cycles of Docetaxel with no dose reductions within 10 weeks. | up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the toxicities of Docetaxel administered before or after doxorubicin/cyclophosphamide(AC). |  | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adjuvant Trial, Dose-Dense, Axillary Node-Positive