Neoadjuvant Chemotherapy + Herceptin in HER2 Positive Stage II-III Breast Cancer Patients

Pilot Trial of Sequential Dose-Dense Neoadjuvant Chemotherapy Plus 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 Overview

• Status: Completed
• Conditions: Breast Neoplasm
• Intervention / Treatment: Drug: epirubicin; Drug: cyclophosphamide; Drug: docetaxel; Drug: trastuzumab

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Advanced Medical Specialties
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Augusta Oncology Associates
    • Macon, Georgia, United States, 31201
      • Cental Georgia Cancer Care
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, PC
  • Montana
    • Billings, Montana, United States, 59101
      • Hematology Oncology Centers of the Northern Rockies, PC
  • New York
    • Great Neck, New York, United States, 11021
      • Arena Oncology Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The West Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

Drug: epirubicin; epirubicin (100 mg/m^2) every 2 weeks for 4 cycles; Other Names: Ellence®; Drug: cyclophosphamide; cyclophosphamide (600 mg/m^2) every 2 weeks for 4 cycles; Other Names: Cytoxan; Drug: docetaxel; docetaxel (75 mg/m^2) every 2 weeks for 4 cycles; Other Names: Taxotere®; Drug: trastuzumab; trastuzumab (6 mg/kg [loading dose] once then 4 mg/kg [maintenance dose]) every 2 weeks for 4 treatments; Other Names: Herceptin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Able to Complete > 85% of the Planned Dose on Schedule	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.	From the start of treatment through the neoadjuvant treatment period (approximately 20 weeks)
Frequency of Grade 3 or 4 Hematologic and Nonhematologic Toxicities	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.	Toxicities are evaluated every 2 weeks during neoadjuvant treatment and assessed once during the post-treatment follow-up period, up to 25 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Response	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.	At completion of neoadjuvant treatment period, up to 24 weeks.
Clinical Response Prior to Surgery	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.	Assessed every 2 weeks during neoadjuvant treatment and prior to definitive surgery, up to 23 weeks.
Left Ventricular Ejection Fraction (LVEF)	LVEF was assessed by echocardiogram (ECHO) or multigated angiogram (MUGA) during neoadjuvant treatment and during follow-up.	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 is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.	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)	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.	Measured from day 1 of treatment until time of death, assessed up to 48 months.

Collaborators and Investigators

• Sponsor: Accelerated Community Oncology Research Network
• Collaborators: Aventis Pharmaceuticals
• Investigators: Study Chair: Lee S Schwartzberg, MD, FACP, Accelerated Community Oncology Research Network, Inc. (ACORN)

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: December 28, 2005
• First Submitted That Met QC Criteria: December 28, 2005
• First Posted (Estimate): December 29, 2005

Study Record Updates

• Last Update Posted (Estimate): March 20, 2012
• Last Update Submitted That Met QC Criteria: March 15, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: neoadjuvant chemotherapy; HER2 positive breast cancer; stage II - III breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Trastuzumab; Epirubicin
• Other Study ID Numbers: ACORN ALSSNBC0401