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

This study has been completed.
Sponsor:
Collaborator:
Aventis Pharmaceuticals
Information provided by (Responsible Party):
Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:
NCT00270894
First received: December 28, 2005
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

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)

Condition Intervention Phase
Breast Neoplasm
Drug: epirubicin
Drug: cyclophosphamide
Drug: docetaxel
Drug: trastuzumab
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Accelerated Community Oncology Research Network:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 30
Study Start Date: November 2005
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Ellence®
Drug: cyclophosphamide
cyclophosphamide (600 mg/m^2) every 2 weeks for 4 cycles
Other Name: Cytoxan
Drug: 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®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00270894

Locations
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
Sponsors and Collaborators
Accelerated Community Oncology Research Network
Aventis Pharmaceuticals
Investigators
Study Chair: Lee S Schwartzberg, MD, FACP Accelerated Community Oncology Research Network, Inc. (ACORN)
  More Information

No publications provided

Responsible Party: Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier: NCT00270894     History of Changes
Other Study ID Numbers: ACORN ALSSNBC0401
Study First Received: December 28, 2005
Results First Received: November 18, 2011
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Accelerated Community Oncology Research Network:
neoadjuvant chemotherapy
HER2 positive breast cancer
stage II - III breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Trastuzumab
Cyclophosphamide
Epirubicin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014