Chemotherapy Followed by Surgery in Treating Women With Stage II or Stage III Breast Cancer
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|ClinicalTrials.gov Identifier: NCT00003953|
Recruitment Status : Completed
First Posted : April 28, 2004
Last Update Posted : January 28, 2013
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of doxorubicin and docetaxel followed by surgery in treating women who have stage II or stage III breast cancer.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Biological: filgrastim Drug: CMF regimen Drug: docetaxel Drug: doxorubicin hydrochloride Drug: tamoxifen citrate Procedure: autologous bone marrow transplantation Procedure: surgical procedure Radiation: radiation therapy||Phase 2|
OBJECTIVES: I. Determine the clinical and pathological response of women with stage II-IIIB primary breast cancer to preoperative high dose chemotherapy with sequential doxorubicin and docetaxel. II. Determine the safety and toxicity of this regimen in these patients. III. Determine the rate of breast conservation surgery in these patients on this regimen. IV. Determine the clinical response of these patients to docetaxel after 3 courses of doxorubicin. V. Correlate any circulating tumor cells shed at time of surgery with clinical response and pathological findings in these patients. VI. Determine whether tumor response correlates with HER2/neu expression of the primary tumor.
OUTLINE: Patients receive doxorubicin IV on days 1, 15, and 29, followed by docetaxel IV over 1 hour on days 43, 57, and 71. Filgrastim (G-CSF) is administered subcutaneously on days 3-10 of each 2 week course. Fourteen to 21 days following preoperative chemotherapy, patients undergo a radical, modified radical, or breast sparing surgery plus axillary lymph node dissection. Patients with disease progression or inoperable stage IIIB disease are removed from study. Following surgery, patients are stratified into one of three postoperative regimens: Stratum I: Patients with 0 lymph node metastases receive no further chemotherapy or receive cyclophosphamide, methotrexate, and fluorouracil (CMF) for 4 courses. Stratum II: Patients with 1-3 lymph node metastases receive CMF for 4 courses. Stratum III: Patients with at least 4 lymph node metastases or stage IIIB may receive high dose chemotherapy with stem cell support. Two to 6 weeks after surgery, patients undergoing breast sparing procedure receive adjuvant radiotherapy. Patients undergoing mastectomy receive chest wall and supraclavicular radiotherapy if initial clinical stage is T3, T4, or N2. All other patients with N1 with greater than 4 lymph nodes and N3 should receive radiotherapy. Radiotherapy is administered 5 days a week for 5.5 weeks. Patients with positive estrogen or progesterone receptors receive oral tamoxifen daily for 5 years. Patients are followed every 3 months for 3 years, then every 6 months for 5 years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 27-35 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Preoperative Dose-Dense Chemotherapy With Sequential Doxorubicin and Docetaxel for Initial Treatment of Operable and Inoperable Stage II-IIIB Breast Cancer|
|Study Start Date :||February 1999|
|Actual Primary Completion Date :||November 2001|
|Actual Study Completion Date :||January 2013|
|Experimental: Doxorubicin and Docetaxel||
Filgrastim (G-CSF) is administered subcutaneously on days 3-10 of each 2 week course.
Drug: CMF regimen
Stratum I and II: receive cyclophosphamide, methotrexate, and fluorouracil (CMF) for 4 courses
Docetaxel IV over 1 hour on days 43, 57, and 71.
Drug: doxorubicin hydrochloride
Doxorubicin IV on days 1, 15, and 29.
Drug: tamoxifen citrate
Patients with positive estrogen or progesterone receptors receive oral tamoxifen daily for 5 years.
Procedure: autologous bone marrow transplantation
Stratum III:may receive high dose chemotherapy with stem cell support
Procedure: surgical procedure
Fourteen to 21 days following preoperative chemotherapy, patients undergo a radical, modified radical, or breast sparing surgery plus axillary lymph node dissection.
Radiation: radiation therapy
Radiotherapy is administered 5 days a week for 5.5 weeks.
- Determine the clinical response of these patients to treatment [ Time Frame: after 3 courses (12 weeks) ]A clinical evaluation of tumor size includes repeat measurements of the palpable tumor in 2 dimensions, repeat mammography, if originally informative, of the affected breast with measurements of the palpable tumor in 2 or 3 dimensions and/or, evaluation of ipsilateral axillary lymph nodes with measurements, if palpable.
- Pathological Response [ Time Frame: after surgery at 15 weeks ]Number of patients with a complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). CR is defined as disappearance of lesions. PR is defined as at least a 50% reduction in the sum of lesions. SD is defined as no significant change and PD is defined as the increase in the size of lesions.
- Detection of circulating tumor cells [ Time Frame: after surgery at 15 weeks ]Detection of circulating tumor cells will be done using a panel of immunocytochemical antibodies directed against breast cancer epithelial cells and IMPATH/BIS laboratories. This assay can detect as few as 1 in 5x105 circulating tumor cells
- Tumor response correlates with HER2/neu expression of the primary tumor. [ Time Frame: baseline ]Pretreatment core needle biopsies will be analyzed for expression of HER2/neu expression using immunohistochemical staining.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003953
|United States, Ohio|
|Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|Metro Health Medical Center|
|Cleveland, Ohio, United States, 44109|
|Study Chair:||Brenda W. Cooper, MD||Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|