Neoadjuvant Chemotherapy + Herceptin in HER2 Positive Stage II-III Breast Cancer Patients
The purpose of this study is to evaluate the effectiveness and tolerability of the combination of the following medications given every two weeks in HER2 positive breast cancer patients:
- trastuzumab (Herceptin)
- epirubicin (Ellence)
- cyclophosphamide (Cytoxan)
- docetaxel (Taxotere)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Trial of Sequential Dose-Dense Neoadjuvant Chemotherapy Plus Herceptin in HER2 Positive Stage II-III Breast Cancer Patients|
- Percentage of Subjects Able to Complete > 85% of the Planned Dose on Schedule [ Time Frame: From the start of treatment through the neoadjuvant treatment period (approximately 20 weeks) ] [ Designated as safety issue: No ]Feasibility will be determined by evaluating the percentage of subjects able to complete the neoadjuvant portion of the study on time with > 85% of the protocol-specified dose.
- Frequency of Grade 3 or 4 Hematologic and Nonhematologic Toxicities [ Time Frame: Toxicities are evaluated every 2 weeks during neoadjuvant treatment and assessed once during the post-treatment follow-up period, up to 25 weeks. ] [ Designated as safety issue: Yes ]Toxicities are evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. Grade refers to the severity of the adverse event (AE). Generally, grade 1 = mild AE; grade 2 = moderate AE; grade 3 = severe AE; grade 4 = life-threatening or disabling AE; grade 5 = death related to AE.
- Pathologic Response [ Time Frame: At completion of neoadjuvant treatment period, up to 24 weeks. ] [ Designated as safety issue: No ]Pathologic response was assessed at time of definitive surgery, scheduled to occur 20-24 weeks after study treatment start. Pathologic complete response was defined as no invasive carcinoma in surgical specimen of breast, but residual ductal carcinoma in situ may be present. Pathologic partial response was defined as >= 50% decrease in sum of diameters in pathologic cancer size compared to pretreatment clinical size. Stable disease was defined as < 50% decrease in sum of diameters in pathologic cancer size compared to pretreatment clinical size, and < 25% increase in sum of diameters.
- Clinical Response Prior to Surgery [ Time Frame: Assessed every 2 weeks during neoadjuvant treatment and prior to definitive surgery, up to 23 weeks. ] [ Designated as safety issue: No ]Clinical response was assessed via physical exam every 2 weeks during neoadjuvant treatment and via imaging prior to definitive surgery. Clinical complete response was defined as no evidence of cancer in breast by exam or imaging. Clinical partial response was defined as >= 50 % reduction in sum of diameters to measurement of primary lesion compared to pretreatment by exam or imaging. Clinical stable disease was defined as < 50% reduction in sum of diameters to measurement of primary lesion compared to pretreatment by exam or imaging, and < 25% increase in sum of diameters.
- Left Ventricular Ejection Fraction (LVEF) [ Time Frame: At screening, prior to cycle 5, prior to surgery, and then during follow-up at Month 6, 12, 24, and 36 ] [ Designated as safety issue: Yes ]LVEF was assessed by echocardiogram (ECHO) or multigated angiogram (MUGA) during neoadjuvant treatment and during follow-up.
- Progression-free Survival (PFS) [ Time Frame: PFS was measured from day 1 of treatment until time of progression or death, whichever comes first, assessed up to 48 months. ] [ Designated as safety issue: No ]PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
- Overall Survival (OS) [ Time Frame: Measured from day 1 of treatment until time of death, assessed up to 48 months. ] [ Designated as safety issue: No ]Overall survival is defined as the time from treatment start until death from any cause. The median overall survival time is used to measure OS.
|Study Start Date:||November 2005|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: Neoadjuvant therapy
Neoadjuvant therapy will consist of epirubicin (100 mg/m^2) + cyclophosphamide (600 mg/m^2) every 2 weeks for 4 cycles; followed by a 3-week break; followed by docetaxel (75 mg/m^2) every 2 weeks for 4 cycles + trastuzumab (6 mg/kg [loading dose] once then 4 mg/kg [maintenance dose]) every 2 weeks for 4 treatments.
epirubicin (100 mg/m^2) every 2 weeks for 4 cycles
Other Name: Ellence®Drug: cyclophosphamide
cyclophosphamide (600 mg/m^2) every 2 weeks for 4 cycles
Other Name: CytoxanDrug: docetaxel
docetaxel (75 mg/m^2) every 2 weeks for 4 cycles
Other Name: Taxotere®Drug: trastuzumab
trastuzumab (6 mg/kg [loading dose] once then 4 mg/kg [maintenance dose]) every 2 weeks for 4 treatments
Other Name: Herceptin®
This is an investigator-initiated, Phase II, non-randomized, single-arm, prospective treatment study. The study will consist of neoadjuvant treatment period (weeks 1 to 20), surgical evaluation period (weeks 20 to 24), and a post-surgical/follow-up period (approximately 3 years). Subjects will be treated on an outpatient basis.
Neoadjuvant therapy will consist of epirubicin + cyclophosphamide given every 2 weeks for four cycles followed by a three week break. Subjects will then receive docetaxel every two weeks for four cycles + trastuzumab (one loading dose) then maintenance dose every 2 weeks for 4 treatments.
|United States, Florida|
|Advanced Medical Specialties|
|Miami, Florida, United States, 33176|
|United States, Georgia|
|Augusta Oncology Associates|
|Augusta, Georgia, United States, 30901|
|Cental Georgia Cancer Care|
|Macon, Georgia, United States, 31201|
|Northwest Georgia Oncology Centers, PC|
|Marietta, Georgia, United States, 30060|
|United States, Montana|
|Hematology Oncology Centers of the Northern Rockies, PC|
|Billings, Montana, United States, 59101|
|United States, New York|
|Arena Oncology Associates|
|Great Neck, New York, United States, 11021|
|United States, Tennessee|
|The West Clinic|
|Memphis, Tennessee, United States, 38120|
|Study Chair:||Lee S Schwartzberg, MD, FACP||Accelerated Community Oncology Research Network, Inc. (ACORN)|