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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA043703 | U.S. NIH Grant/Contract | View source | |
| CWRU-2198 | Other Identifier | Case Comprehensive Cancer Center | |
| NCI-G99-1537 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doxorubicin and Docetaxel | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| filgrastim | Biological | Filgrastim (G-CSF) is administered subcutaneously on days 3-10 of each 2 week course. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Determine the clinical response of these patients to treatment | 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. | after 3 courses (12 weeks) |
| Pathological Response | 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. | after surgery at 15 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Detection of circulating tumor cells | 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 | after surgery at 15 weeks |
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Eligibility Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brenda W. Cooper, MD | Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Cleveland | Ohio | 44106-5065 | United States |
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| Label | URL |
|---|---|
| Clinical trial summary from the National Cancer Institute's PDQ® database | View source |
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| CMF regimen | Drug | Stratum I and II: receive cyclophosphamide, methotrexate, and fluorouracil (CMF) for 4 courses |
|
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| docetaxel | Drug | Docetaxel IV over 1 hour on days 43, 57, and 71. |
|
| doxorubicin hydrochloride | Drug | Doxorubicin IV on days 1, 15, and 29. |
|
| tamoxifen citrate | Drug | Patients with positive estrogen or progesterone receptors receive oral tamoxifen daily for 5 years. |
|
| autologous bone marrow transplantation | Procedure | Stratum III:may receive high dose chemotherapy with stem cell support |
|
| surgical procedure | Procedure | Fourteen to 21 days following preoperative chemotherapy, patients undergo a radical, modified radical, or breast sparing surgery plus axillary lymph node dissection. |
|
| radiation therapy | Radiation | Radiotherapy is administered 5 days a week for 5.5 weeks. |
|
| Tumor response correlates with HER2/neu expression of the primary tumor. |
Pretreatment core needle biopsies will be analyzed for expression of HER2/neu expression using immunohistochemical staining. |
| baseline |
| Metro Health Medical Center | Cleveland | Ohio | 44109 | United States |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| C034456 | CMF regimen |
| D003520 | Cyclophosphamide |
| D008727 | Methotrexate |
| D005472 | Fluorouracil |
| D000077143 | Docetaxel |
| D004317 | Doxorubicin |
| D013629 | Tamoxifen |
| D013514 | Surgical Procedures, Operative |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D013812 | Therapeutics |
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