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

Breast Neoplasm Clinical Trial

Official title:

Pilot Trial of Sequential Dose-Dense Neoadjuvant Chemotherapy Plus Herceptin in HER2 Positive Stage II-III Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00270894
• Other study ID #: ACORN ALSSNBC0401
• Status: Completed
• Phase: Phase 2
• First received: December 28, 2005
• Last updated: March 15, 2012
• Start date: November 2005
• Est. completion date: August 2011

Study information

• Verified date: March 2012
• Source: Accelerated Community Oncology Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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)

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 information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasm
• Breast Neoplasms

Intervention

Drug:
• epirubicin
epirubicin (100 mg/m^2) every 2 weeks for 4 cycles
• cyclophosphamide
cyclophosphamide (600 mg/m^2) every 2 weeks for 4 cycles
• docetaxel
docetaxel (75 mg/m^2) every 2 weeks for 4 cycles
• trastuzumab
trastuzumab (6 mg/kg [loading dose] once then 4 mg/kg [maintenance dose]) every 2 weeks for 4 treatments

Locations

Country	Name	City	State
United States	Augusta Oncology Associates	Augusta	Georgia
United States	Hematology Oncology Centers of the Northern Rockies, PC	Billings	Montana
United States	Arena Oncology Associates	Great Neck	New York
United States	Cental Georgia Cancer Care	Macon	Georgia
United States	Northwest Georgia Oncology Centers, PC	Marietta	Georgia
United States	The West Clinic	Memphis	Tennessee
United States	Advanced Medical Specialties	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Accelerated Community Oncology Research Network	Aventis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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.	Yes
Secondary	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.	No
Secondary	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.	No
Secondary	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	Yes
Secondary	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.	No
Secondary	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.	No