Paclitaxel and Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Patients With Previously Untreated Stage I-III Breast Cancer
Estrogen Receptor-negative Breast Cancer
Estrogen Receptor-positive Breast Cancer
HER2-negative Breast Cancer
HER2-positive Breast Cancer
Progesterone Receptor-negative Breast Cancer
Progesterone Receptor-positive Breast Cancer
Stage IA Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Triple-negative Breast Cancer
Procedure: therapeutic conventional surgery
Radiation: radiation therapy
Drug: doxorubicin hydrochloride
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Neoadjuvant Chemotherapy With and Without Trastuzumab in Patients With Breast Cancer|
- pCR, determined from the surgical specimen and is defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]The pCR rates and exact one-sided 80% confidence intervals will be calculated. The primary analysis is based on the full analysis set (all treated patients). The pCR rates will be summarized overall and for HER+ and HER- subsets.
- Overall incidence and severity of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]Adverse events will be tallied for overall frequency (number and percentage of subjects), worst reported severity, and relationship to study drugs. Serious adverse events will be summarized similarly. Listings of deaths, serious adverse events (SAEs) and adverse events (AEs) leading to early termination of study treatment or premature withdrawal from study will also be provided. Analyses will be reported overall and for HER+ and HER- subsets.
- Clinical complete response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Failure-free survival (FFS) [ Time Frame: The time from the date of administration of study drug to the date of first appearance of tumor lesions by imaging, or death, assessed up to 2 years ] [ Designated as safety issue: No ]The analysis will be based on Kaplan-Meier estimates. FFS will be summarized overall and for HER+ and HER- subsets.
- Overall survival (OAS) [ Time Frame: The time from the date of the date of administration of study drug to the date of death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]The analysis will be based on Kaplan-Meier estimates. OAS will be summarized overall and for HER+ and HER- subsets.
- Identification of gene expression profile signatures that correlate with clinical response as measured by pCR [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]The number of the identified mutated genes, the frequency of each gene being validated by reverse transcriptase-polymerase chain reaction (RT-PCR)/Sanger sequencing method, and the functions of these identified genes will be descriptively summarized.
|Study Start Date:||December 2012|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy, surgery, post-operative therapy)
See Detailed Description
Other Names:Drug: cyclophosphamide
Other Names:Biological: trastuzumab
Other Names:Procedure: therapeutic conventional surgery
Undergo mastectomy or breast conserving surgeryRadiation: radiation therapy
Other Names:Drug: doxorubicin hydrochloride
Other Names:Other: laboratory biomarker analysis
I. To evaluate the toxicities and tolerability of a neoadjuvant dose-dense regimen cyclophosphamide and paclitaxel with or without trastuzumab/radiation therapy (as clinically indicated) in patients with newly diagnosed stage T1cN0 and II-III breast cancer; followed by maintenance trastuzumab in human epidermal growth factor receptor 2 (HER2) positive OR Adriamycin (doxorubicin hydrochloride) followed by radiation therapy (RT) in stage II-III triple negative HER2 (-), estrogen receptor (ER) (-), progesterone receptor (PR) (-) stage T1cN0 and II-III breast cancer patients.
II. To determine the pathological complete response rate (pCR) of this treatment regimen.
III. To identify possible gene expression profile signatures from whole genome array analysis that correlate with clinical response/resistance to chemotherapy as measured by pathologic complete response rate (pCR).
NEOADJUVANT THERAPY: Patients receive paclitaxel intravenously (IV) over 3 hours and cyclophosphamide IV over 1 hour on day 1. Patients with HER2-positive cancer also receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients without metastasis undergo mastectomy or breast conserving surgery 4-8 weeks later.
HER2-POSITIVE PATIENTS: Patients receive standard radiation therapy. Patients also receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
ER/PR POSITIVE PATIENTS: Patients receive standard adjuvant hormonal or endocrine therapy.
STAGE T1cN0 TRIPLE NEGATIVE PATIENTS: Patients receive standard radiation therapy.
STAGE II-III TRIPLE NEGATIVE PATIENTS: Patients receive doxorubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard radiation therapy.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01750073
|Contact: Mary Mailliard, RN BSN OCNemail@example.com|
|Contact: Lisa Houdesheldt, BS CCRPfirstname.lastname@example.org|
|United States, Nebraska|
|Saint Francis Medical Center||Recruiting|
|Grand Island, Nebraska, United States, 68803|
|Contact: Mehmet S. Copur, M.D. 308-398-6518 email@example.com|
|Contact: Clinical Research Staff 308-398-6518 firstname.lastname@example.org|
|Principal Investigator: Mehmet S. Copur, M.D.|
|University of Nebraska Medical Center||Recruiting|
|Omaha, Nebraska, United States, 68198-7830|
|Contact: Elizabeth C. Reed, M.D. 402-559-5388 email@example.com|
|Contact: Mary J. Mailliard, RN BSN OCN 402-559-5582 firstname.lastname@example.org|
|Principal Investigator: Elizabeth C. Reed|
|Principal Investigator:||Elizabeth Reed||University of Nebraska|