Pilot Trial of Sequential Dose-Dense Neoadjuvant Chemotherapy Plus Herceptin in HER2 Positive Stage II-III Breast Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- epirubicin
- Conditions
- Breast Neoplasm
- Sponsor
- Accelerated Community Oncology Research Network
- Enrollment
- 30
- Locations
- 7
- Primary Endpoint
- Percentage of Subjects Able to Complete > 85% of the Planned Dose on Schedule
- Status
- Completed
- Last Updated
- 14 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: epirubicin
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.
Intervention: cyclophosphamide
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.
Intervention: docetaxel
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.
Intervention: trastuzumab
Outcomes
Primary Outcomes
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)
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.
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 Outcomes
- Pathologic Response(At completion of neoadjuvant treatment period, up to 24 weeks.)
- Clinical Response Prior to Surgery(Assessed every 2 weeks during neoadjuvant treatment and prior to definitive surgery, up to 23 weeks.)
- 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)
- 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.)
- Overall Survival (OS)(Measured from day 1 of treatment until time of death, assessed up to 48 months.)