Neoadjuvant Chemotherapy + Herceptin in HER2 Positive Stage II-III Breast Cancer Patients
- Conditions
- Breast Neoplasm
- Interventions
- Registration Number
- NCT00270894
- Lead Sponsor
- Accelerated Community Oncology Research Network
- Brief Summary
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)
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 30
- Non-pregnant females =/> 18 years of age
- Non-inflammatory breast cancer stage IIA - IIIC or high risk node negative
- Core biopsy of breast demonstrating invasive cancer and documented ER/PgR receptor status
- Normal cardiac function and adequate hematologic function
- Human epidermal growth factor receptor 2 protein (HER2) positive
- No evidence of metastatic disease
- ECOG Performance Status 0 - 1
- Women of childbearing potential must agree to using effective contraception while on treatment and for at least 3 months post-treatment
- Treated with other investigational drugs within 30 days
- Uncontrolled intercurrent disease or active infection
- Known sensitivity to e. coli-derived proteins or polysorbate 80
- Psychiatric illness or social situation that would limit study compliance
- Pre-existing peripheral neuropathy > Grade 1
- Cancer within 5 years of screening with the exception of surgically cured nonmelanomatous skin cancer; in-situ carcinoma of the cervix; or in-situ carcinoma of the breast
- Bilateral synchronous breast cancer
- Inflammatory breast cancer
- Women who are pregnant or breast feeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Neoadjuvant therapy docetaxel 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. Neoadjuvant therapy epirubicin 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. Neoadjuvant therapy cyclophosphamide 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. Neoadjuvant therapy trastuzumab 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.
- Primary Outcome Measures
Name Time Method Percentage of Subjects Able to Complete > 85% of the Planned Dose on Schedule From the start of treatment through the neoadjuvant treatment period (approximately 20 weeks) 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 Toxicities are evaluated every 2 weeks during neoadjuvant treatment and assessed once during the post-treatment follow-up period, up to 25 weeks. 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.
- Secondary Outcome Measures
Name Time Method Pathologic Response At completion of neoadjuvant treatment period, up to 24 weeks. 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 Assessed every 2 weeks during neoadjuvant treatment and prior to definitive surgery, up to 23 weeks. 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) At screening, prior to cycle 5, prior to surgery, and then during follow-up at Month 6, 12, 24, and 36 LVEF was assessed by echocardiogram (ECHO) or multigated angiogram (MUGA) during neoadjuvant treatment and during follow-up.
Progression-free Survival (PFS) PFS was measured from day 1 of treatment until time of progression or death, whichever comes first, assessed up to 48 months. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
Overall Survival (OS) Measured from day 1 of treatment until time of death, assessed up to 48 months. 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.
Trial Locations
- Locations (7)
Arena Oncology Associates
🇺🇸Great Neck, New York, United States
Advanced Medical Specialties
🇺🇸Miami, Florida, United States
Northwest Georgia Oncology Centers, PC
🇺🇸Marietta, Georgia, United States
The West Clinic
🇺🇸Memphis, Tennessee, United States
Augusta Oncology Associates
🇺🇸Augusta, Georgia, United States
Cental Georgia Cancer Care
🇺🇸Macon, Georgia, United States
Hematology Oncology Centers of the Northern Rockies, PC
🇺🇸Billings, Montana, United States