Adj TC + Herceptin Early Stage Breast Cancer

NCT ID: NCT00493649

Last Updated: 2016-11-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

493 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2013-04-30

Brief Summary

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The purpose of this research study is to find out what effects (good and bad) docetaxel/cyclophosphamide (brand names: Taxotere and Cytoxan, or TC) plus trastuzumab (brand name: Herceptin, or H) has HER2+ breast cancer.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TC+H

On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel (Taxotere) 75 mg/m2 IV (over 1 hour), plus cyclophosphamide (Cytoxan) 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab (Herceptin) 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter.

Group Type EXPERIMENTAL

Taxotere

Intervention Type DRUG

On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.

Cytoxan

Intervention Type DRUG

On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.

Herceptin

Intervention Type DRUG

On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.

Interventions

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Taxotere

On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.

Intervention Type DRUG

Cytoxan

On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.

Intervention Type DRUG

Herceptin

On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.

Intervention Type DRUG

Other Intervention Names

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docetaxel cyclophosphamide trastuzumab

Eligibility Criteria

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Inclusion Criteria

A woman will be eligible for inclusion in this study if she meets all of the following criteria:

* Has HER2+ (IHC staining of 3+ \[uniform, intense membrane staining of \>30% of invasive tumor cells\], or a FISH result of .6 HER2 gene copies per nucleus or a FISH ratio \[HER2 gene signals to chromosome 17 signals\] of \>2.2; patients with equivocal FISH ratio results 1.8-2.2 are also eligible if 3+ IHC) (Appendix IX); Stage I, IIA, IIB, or IIIA T1-3N1-3M0 disease. At the discretion of the Treating Physician, patients with 4+ nodes with other factors such as patient choice, older age, preexisting cardiac disease with normal MUGA or ECHO may be enrolled into a separate subgroup.
* Has operable, histologically confirmed, invasive carcinoma of the breast.
* Has known ER and PR status
* Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix VII)
* Has had no prior chemotherapy unless it was given \>5 years ago for breast cancer or other cancer
* Has an ECOG Performance Status (PS) 0-1
* Age \>18 to \<70 years old.
* Has laboratory values of: See protocol for specific details
* Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase (ALP) within the ranges shown below. In determining eligibility the more abnormal of the 2 values (AST or ALT) should be used. See protocol for specific details
* Has complete surgical resection of the primary breast tumor: either lumpectomy or mastectomy with sentinel lymph node or axillary dissection.
* It has been \<84 days since the date of definitive surgery, and there is adequate wound healing as determined by the Treating Physician
* Has no evidence of metastatic disease by physical examination and x-ray; appropriate scans as needed by each individual patient (eg, bone scan; abdominal, chest CT; PET or PET/CT; ultrasound; or MRI should indicate no evidence of metastatic disease.
* Has normal cardiac function as evidenced by a LVEF \>50%, but must be within normal limits (WNL) by institutional standard, as determined by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO). The same modality must be used throughout the study to evaluate LVEF. Ejection fraction (EF) as determined by ECHO must be WNL by institutional standard.
* Has a negative serum pregnancy test within 7 calendar days prior to registration (female patients of childbearing potential \[not surgically sterilized and between menarche and 1 year postmenopause\]).
* If fertile, patient has agreed to use an acceptable method of birth control (barrier contraceptive) to avoid pregnancy for the duration of the study and for a period of 3 months thereafter
* Has signed a Patient Informed Consent Form
* Has signed a Patient Authorization Form

Exclusion Criteria

A woman will be excluded from this study if she meets any of the following criteria:

* Has any evidence of disease following complete surgical resection of the primary tumor and metastatic workup
* Has Stage IIIB breast cancer (T4 disease; ie, patients with fixed tumors, peau d'orange skin changes, skin ulcerations, or inflammatory changes).
* Has Stage IV breast cancer (M1 disease on TNM staging system)
* Had prior chemotherapy for breast cancer or other cancer within the last 5 years (no neoadjuvant chemotherapy in this study is permitted)
* Has a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80
* Has had a myocardial infarction (MI) within 6 months of trial enrollment, or has New York Heart Association (NYHA) Class II or greater heart failure (see Appendix III), uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic changes
* Has abnormal baseline MUGA (or ECHO) (\<50%, or less than institutional LLN)
* Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Adjuvant hormonal therapy, if needed, may be given during radiation therapy and during treatment with trastuzumab after completion of chemotherapy.
* Is receiving concurrent investigational therapy or has received such therapy within the past 30 calendar days
* Has peripheral neuropathy \>Grade 1
* Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious viral (including clinically defined AIDS), bacterial or fungal infection; or history of uncontrolled seizures, or diabetes, or CNS disorders deemed by the Treating Physician to be clinically significant, precluding informed consent
* Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive
* Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs
* Is an obese patient to whom the Treating Physician would not be comfortable administering full doses of study drugs as calculated by the BSA. Obese patients will be treated based on actual body weight. Obese patients treated with full doses based on actual BSA are eligible
* Is a pregnant or breastfeeding woman
* Is deemed unable to comply with requirements of study
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

US Oncology Research

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen E Jones, MD

Role: PRINCIPAL_INVESTIGATOR

US Oncology Research

Locations

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Birmingham Hematology and Oncology

Birmingham, Alabama, United States

Site Status

Hematology Oncology Associates

Phoenix, Arizona, United States

Site Status

Northern AZ Hematology & Oncology Associates

Sedona, Arizona, United States

Site Status

Arizona Oncology Associates DBA HOPE

Tucson, Arizona, United States

Site Status

Rocky Mountain Cancer Center-Rose

Denver, Colorado, United States

Site Status

Connecticut Oncology & Hematology, LLP

Torrington, Connecticut, United States

Site Status

Florida Cancer Institute

New Port Richey, Florida, United States

Site Status

Ocala Oncology Center

Ocala, Florida, United States

Site Status

Cancer Centers of Florida, P.A.

Ocoee, Florida, United States

Site Status

Hematology Oncology Associates of IL

Chicago, Illinois, United States

Site Status

Cancer Care & Hematology Specialists of Chicagoland

Niles, Illinois, United States

Site Status

Central Indiana Cancer Centers

Indianapolis, Indiana, United States

Site Status

Hope Center

Terre Haute, Indiana, United States

Site Status

Kansas City Cancer Centers-Southwest

Overland Park, Kansas, United States

Site Status

Maryland Oncology Hematology, P.A.

Columbia, Maryland, United States

Site Status

Alliance Hematology Oncology P.A.

Westminster, Maryland, United States

Site Status

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, United States

Site Status

Missouri Cancer Associates

Columbia, Missouri, United States

Site Status

Arch Medical Services, Inc.

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Site Status

Hematology-Oncology Associates of NNJ, P.A.

Morristown, New Jersey, United States

Site Status

New Mexico Cancer Care Associates

Santa Fe, New Mexico, United States

Site Status

New York Oncology Hematology, P.C.

Albany, New York, United States

Site Status

Ruth Oratz MD

New York, New York, United States

Site Status

Interlakes Oncology Hematology, PC

Rochester, New York, United States

Site Status

Cancer Centers of North Carolina

Raleigh, North Carolina, United States

Site Status

Greater Dayton Cancer Center

Kettering, Ohio, United States

Site Status

Willamette Valley Cancer Center

Eugene, Oregon, United States

Site Status

Medical Oncology Associates

Kingston, Pennsylvania, United States

Site Status

Cancer Centers of the Carolinas

Greenville, South Carolina, United States

Site Status

Texas Cancer Center-Abilene (South)

Abilene, Texas, United States

Site Status

Texas Oncology, P.A.-Amarillo

Amarillo, Texas, United States

Site Status

Texas Cancer Center

Arlington, Texas, United States

Site Status

Texas Oncology Cancer Center

Austin, Texas, United States

Site Status

Mamie McFaddin Ward Cancer Center

Beaumont, Texas, United States

Site Status

Texas Oncology, P.A.-Bedford

Bedford, Texas, United States

Site Status

Texas Cancer Center at Medical City

Dallas, Texas, United States

Site Status

Texas Oncology, P.A.

Dallas, Texas, United States

Site Status

Methodist Charlton Cancer Ctr.

Dallas, Texas, United States

Site Status

Texas Oncology, P.A.

Dallas, Texas, United States

Site Status

Texas Cancer Center

Denton, Texas, United States

Site Status

El Paso Cancer Treatment Ctr

El Paso, Texas, United States

Site Status

Texas Oncology, P.A.

Fort Worth, Texas, United States

Site Status

Texas Oncology, P.A.

Garland, Texas, United States

Site Status

Texas Oncology, P.A.

Houston, Texas, United States

Site Status

Lake Vista Cancer Center

Lewisville, Texas, United States

Site Status

Longview Cancer Center

Longview, Texas, United States

Site Status

South Texas Cancer Center-McAllen

McAllen, Texas, United States

Site Status

Texas Cancer Center of Mesquite

Mesquite, Texas, United States

Site Status

Allison Cancer Center

Midland, Texas, United States

Site Status

Texas Oncology-Odessa

Odessa, Texas, United States

Site Status

Paris Regional Cancer Center

Paris, Texas, United States

Site Status

San Antonio Tumor and Blood Clinic

San Antonio, Texas, United States

Site Status

HOAST-Medical Dr.

San Antonio, Texas, United States

Site Status

Texas Cancer Center-Sherman

Sherman, Texas, United States

Site Status

Texas Oncology Cancer Center-Sugar Land

Sugar Land, Texas, United States

Site Status

Tyler Cancer Center

Tyler, Texas, United States

Site Status

Texas Oncology Cancer Care and Research

Waco, Texas, United States

Site Status

Texas Oncology PA

Webster, Texas, United States

Site Status

Texoma Cancer Center

Wichita Falls, Texas, United States

Site Status

Fairfax Northern VA Hem-Onc PC

Fairfax, Virginia, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Onc and Hem Associates of SW VA, Inc.

Salem, Virginia, United States

Site Status

Highline Medical Oncology

Burien, Washington, United States

Site Status

Puget Sound Cancer Center-Edmonds

Edmonds, Washington, United States

Site Status

Puget Sound Cancer Center-Seattle

Seattle, Washington, United States

Site Status

Cancer Care Northwest-South

Spokane, Washington, United States

Site Status

Northwest Cancer Specialists-Vancouver

Vancouver, Washington, United States

Site Status

Yakima Valley Mem Hosp/North Star Lodge

Yakima, Washington, United States

Site Status

Countries

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United States

References

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Jones SE, Collea R, Paul D, Sedlacek S, Favret AM, Gore I Jr, Lindquist DL, Holmes FA, Allison MAK, Brooks BD, Portillo RM, Vukelja SJ, Steinberg MS, Stokoe C, Crockett MW, Wang Y, Asmar L, Robert NJ, O'Shaughnessy J. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol. 2013 Oct;14(11):1121-1128. doi: 10.1016/S1470-2045(13)70384-X. Epub 2013 Sep 3.

Reference Type DERIVED
PMID: 24007746 (View on PubMed)

Other Identifiers

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11270

Identifier Type: OTHER

Identifier Source: secondary_id

06-038

Identifier Type: -

Identifier Source: org_study_id