Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery
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|ClinicalTrials.gov Identifier: NCT00194779|
Recruitment Status : Completed
First Posted : September 19, 2005
Results First Posted : March 12, 2018
Last Update Posted : March 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor-negative Breast Cancer Estrogen Receptor-positive Breast Cancer HER2-positive Breast Cancer Progesterone Receptor-negative Breast Cancer Progesterone Receptor-positive Breast Cancer Stage IA Breast Cancer Stage IB Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer||Drug: doxorubicin hydrochloride Drug: cyclophosphamide Drug: paclitaxel Biological: filgrastim Drug: capecitabine Drug: methotrexate Drug: vinorelbine tartrate Procedure: needle biopsy Procedure: therapeutic conventional surgery Other: immunohistochemistry staining method Biological: trastuzumab Drug: tamoxifen citrate Drug: letrozole Other: laboratory biomarker analysis||Phase 2|
I. To assess the pathologic response rate in patients with operable breast cancer treated with a two part, neoadjuvant regimen consisting of weekly doxorubicin (doxorubicin hydrochloride) and daily oral cyclophosphamide given with G-CSF (filgrastim) support for 12 weeks followed weekly paclitaxel for 12 weeks.
I. To assess the clinical response rate in patients with surgically resectable breast cancer treated with weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 12 weeks.
II. To assess the clinical response rate in patients with surgically resectable breast cancer treated with weekly paclitaxel for 12 weeks.
III. To assess the relapse rate, overall and disease-free survival in patients with operable breast cancer treated with neoadjuvant chemotherapy consisting of weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 12 weeks followed weekly paclitaxel for 12 weeks and adjuvant chemotherapy with Xeloda (capecitabine), Methotrexate and Navelbine (vinorelbine tartrate) (XMN).
IV. To assess the toxicity associated with these regimens. V. To assess whether the phenotype of breast cancer changes with treatment. VI. To assess whether phenotypic changes in breast tumors predict outcome.
PART I: Patients receive doxorubicin hydrochloride intravenously (IV) on day 1 of each week, cyclophosphamide orally (PO) once daily (QD), and filgrastim subcutaneously (SC) QD on days 2-7 of each week. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.
PART II: Patients* receive paclitaxel IV over 1 hour on day 1 of each week. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo definitive surgical resection by partial mastectomy (lumpectomy) or mastectomy after completion of neoadjuvant chemotherapy.
PART III: Patients** unable to achieve complete pathologic response (pCR) or disease that has been down-staged to =< 1 cm with no positive nodes following surgery receive capecitabine PO twice daily (BID) on days 1-14, methotrexate IV on days 1, 8 and 15, and vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients with HER2/neu-positive disease also receive trastuzumab IV over 30-90 minutes once weekly or every 3 weeks for 1 year beginning in Part II.
NOTE: **Patients with hormone receptor-positive disease also receive tamoxifen PO QD for 5 years (premenopausal) OR letozole PO QD or tamoxifen PO QD for 5 years (postmenopausal) beginning in Part III.
After completion of study treatment, patients are followed up every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study of Weekly Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF Followed by Weekly Paclitaxel as Neoadjuvant Therapy for Resectable, Hormone Receptor Negative or Hormone Receptor Positive, HER-2/Neu Positive Breast Cancer Followed by a Novel Regimen of Capecitabine, Methotrexate and Vinorelbine for Patients Who Do Not Have Either a Macroscopic or Microscopic Pathologic Complete Response, a Phase II Study|
|Study Start Date :||October 2003|
|Actual Primary Completion Date :||June 2010|
|Actual Study Completion Date :||June 2011|
Experimental: Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
Drug: doxorubicin hydrochloride
Drug: vinorelbine tartrate
Procedure: needle biopsy
Procedure: therapeutic conventional surgery
Undergo definitive breast surgery
Other: immunohistochemistry staining method
Other Name: immunohistochemistry
Drug: tamoxifen citrate
Other: laboratory biomarker analysis
- Combined Rate of Microscopic pCR and Macroscopic Pathologic Complete Response (mCR) [ Time Frame: Up to 16 weeks ]
Microscopic pCR: No evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection. mCR: The examining pathologist cannot identify gross residual tumor mass in the surgical specimen. This differs from a pCR where the specimen must also be negative for invasive tumor by microscopy. For this study, we are using a definition of mCR that will make the trial more translatable to other institutions. For this study, mCR will be defined as no focus of invasive cancer >= 1 cm.
Count of participants with either a pCR or mCR.
- Number and Percent of Patients Reporting Grade 2, 3, 4, or Fatal Toxicities of These Regimens, Need for Dose Reduction, or Treatment Interruption or Discontinuation [ Time Frame: From the initiation of study treatments to 30 days after the end of neoadjuvant treatment or adjuvant treatment if received ]
- Correlation of Molecular Markers With Response [ Time Frame: After completion of neoadjuvant therapy ]
- Relapse Rate in Patients With Operable Breast Cancer Treated With Neoadjuvant Chemotherapy for 12 Weeks Followed by Weekly Paclitaxel for 12 Weeks and Adjuvant Chemotherapy [ Time Frame: Up to 8 years ]Count of patients that relapsed.
- Time to Progression [ Time Frame: Up to 5 years ]Median time to progression free survival.
- OS in Patients With Operable Breast Cancer Treated With Neoadjuvant Chemotherapy for 12 Weeks Followed Weekly Paclitaxel for 12 Weeks and Adjuvant Chemotherapy With XMN [ Time Frame: 1, 2, and 5 years ]Kaplan-Meier estimate of overall survival, assessed at 1, 2, and 5 years.
- Disease-free Survival [ Time Frame: 1, 2, and 5 years ]Kaplan-Meier estimate of disease-free survival, assessed at 1, 2, and 5 years.
- Clinical Response to Neoadjuvant Therapy [ Time Frame: Up to 12 weeks ]
- Clinical Response to Paclitaxel [ Time Frame: Up to 24 weeks ]
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): NCT00194779
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Georgiana Ellis||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|