NCT00021255|CompletedPhase 3Results

Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer

Multicenter Phase III Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed By Docetaxel (AC-T) With Doxorubicin and Cyclophosphamide Followed By Docetaxel and Trastuzumab (Herceptin)(AC-TH) and With Docetaxel, Carboplatin and Trastuzumab (TCH) In The Adjuvant Treatment Of Node Positive and High Risk Node Negative Patients With Operable Breast Cancer Containing The HER2 Alteration

Sanofi ClinicalTrials.gov

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2 other identifiers

TAX_GMA_302BCIRG 006

Study Type

interventional

Target

3,222

Locations

38 countries

Sites

Timeline

RegisteredJan 2003

StartedApr 2001

CompletionDec 2014

Brief Summary

Primary objective:

Compare disease-free survival in women with human epidermal growth factor receptor 2 (HER2)-neu-expressing node-positive or high-risk node-negative operable breast cancer treated with adjuvant doxorubicin, cyclophosphamide, and docetaxel with or without trastuzumab (Herceptin) vs trastuzumab, docetaxel, and carboplatin. Secondary objective:
Compare overall survival of participants treated with these regimens.
Compare the toxic effects (including cardiac) of these regimens in these participants.
Compare quality of life of participants treated with these regimens.
Compare pathologic and molecular markers for predicting efficacy of these regimens in these participants.
For substudy: Compare peripheral levels of shed HER2-neu extracellular domain with fluorescence in situ hybridization in predicting outcome in participants treated with these regimens.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

3,222

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Apr 2001

Longer than P75 for phase_3

Geographic Reach

38 countries

38 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

13.7 years study duration

Study Start

First participant enrolled

April 1, 2001

Completed

3 months until next milestone

First Submitted

Initial submission to the registry

July 11, 2001

Completed

1.5 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed

11.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2014

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed

2 years until next milestone

Results Posted

Study results publicly available

November 15, 2016

Completed

Last Updated

November 15, 2016

Status Verified

September 1, 2016

Enrollment Period

13.7 years

First QC Date

July 11, 2001

Results QC Date

June 15, 2016

Last Update Submit

September 26, 2016

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

Percentage of Participants With Disease Free Survival at 5 Years
Disease Free Survival was defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer (with the exception of curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix) or death from any cause whichever occured first. Disease free survival was estimated using the Kaplan-Meier method.
From randomization until relapse or death or up to 5 years

Secondary Outcomes (2)

Percentage of Participants With Disease Free Survival at 10 Years
From randomization until relapse or death or up to 10 years
Overall Survival- Percentage of Participants Who Survived at 10 Years
From randomization until death or up to 10 years

Study Arms (3)

Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T)

EXPERIMENTAL

Doxorubicin 60 mg/m² intravenous (IV) bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus injection on Day 1 of every 3 weeks for 4 cycles followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles.

Drug: DoxorubicinDrug: CyclophosphamideDrug: Docetaxel

AC followed by Docetaxel + Herceptin (AC→TH)

EXPERIMENTAL

Doxorubicin 60 mg/m² IV bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus Injection on Day 1 of every 3 weeks for 4 cycles. Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 5, followed by Herceptin 2 mg/kg by IV infusion weekly starting from Day 8; and docetaxel 100 mg/m² IV infusion on Day 2 of Cycle 5, then on Day 1 of every 3 weeks for all subsequent cycles ( total 4 cycles). After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose.

Drug: DoxorubicinDrug: CyclophosphamideDrug: DocetaxelDrug: Herceptin

Docetaxel + Carboplatin + Herceptin (TCH)

EXPERIMENTAL

Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 1 only, followed by Herceptin 2 mg/kg IV infusion weekly starting from Day 8 until three weeks after the last cycle of chemotherapy. Docetaxel 75 mg/ m² IV infusion on Day 2 of Cycle 1, then on Day 1 of all subsequent cycles followed by carboplatin IV infusion at target AUC = 6 mg/mL/min repeated every 3 weeks for a total of 6 cycles. After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg by IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose.

Drug: DocetaxelDrug: HerceptinDrug: Carboplatin

Interventions

DoxorubicinDRUG

AC followed by Docetaxel + Herceptin (AC→TH)Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T)

CyclophosphamideDRUG

AC followed by Docetaxel + Herceptin (AC→TH)Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T)

DocetaxelDRUG

Also known as: Taxotere

AC followed by Docetaxel + Herceptin (AC→TH)Docetaxel + Carboplatin + Herceptin (TCH)Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T)

HerceptinDRUG

Also known as: Trastuzumab

AC followed by Docetaxel + Herceptin (AC→TH)Docetaxel + Carboplatin + Herceptin (TCH)

CarboplatinDRUG

Docetaxel + Carboplatin + Herceptin (TCH)

Eligibility Criteria

Age18 Years - 70 Years

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the participants for treatment and follow-up.
Accessible for treatment and follow-up at participating centers.
Histologically proven breast cancer with an interval between definitive surgery that included axillary lymph node involvement assessment and registration of less than or equal to 60 days. A central pathology review might be performed post randomization for confirmation of diagnosis and molecular studies. The same block used for HER2neu determination prior to randomization might be used for the central pathology review.
Definitive surgical treatment must be either mastectomy with axillary lymph node involvement assessment, or breast conserving surgery with axillary lymph node involvement assessment for operable breast cancer (T1-3, Clinical N0-1, M0). Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and/or ductal carcinoma in situ (DCIS).
Participants must be either lymph node positive or high risk node negative. Lymph node positive participants were to be defined as participants having invasive adenocarcinoma with at least one axillary lymph node (pN1) showing evidence of tumor among a minimum of six resected lymph nodes. High risk lymph node negative participants were to be defined as participants having invasive adenocarcinoma with either 0 (pNo) among a minimum of 6 resected lymph nodes or negative sentinel node biopsy (pNo) and at least one of the following factors: tumor size \> 2 cm, estrogen receptor (ER) and/or progesteron receptor (PR) status was negative, histologic and/or nuclear grade 2-3, or age \< 35 years.
Tumor must show the presence of the HER2neu gene amplification by Fluorescence In-Situ Hybridization (FISH analysis) by a designated central laboratory.
Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to randomization. Results must be known at the time of randomization.
Karnofsky Performance status index ≥ 80%.
Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF) (multiple-gated acquisition \[MUGA\] scan) and electrocardiogram (ECG) within 3 months prior to registration. The result of the MUGA must be equal to or above the lower limit of normal for the institution.
Laboratory requirements: (within 14 days prior to registration)
a) Hematology: i) Neutrophils ≥ 2.0 109/L ii) Platelets ≥ 100 109/L iii) Hemoglobin ≥ 10 g/Dl
b) Hepatic function: i) Total bilirubin ≤ 1 UNL ii) Aspartate aminotransferase (ASAT) (Serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine amino transferase (ALAT) (Serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 2.5 UNL iii) Alkaline phosphatase ≤ 5 UNL iv) Participants with ASAT and/or ALAT \> 1.5 x UNL associated with alkaline phosphatase \> 2.5 x UNL are not eligible for the study.
c) Renal function: i) Creatinine ≤ 175 µmol/L (2 mg/dL) ii) If creatinine was 140 - 175 μmol/L, the calculated creatinine clearance should be ≥ 60 mL/min.
Complete staging work-up within 3 months prior to registration. All participants had bilateral mammography, chest X-ray (posterioanterior \[PA\] and lateral) and/or computerized tomography (CT) and/or magnetic resonance imaging (MRI), abdominal ultrasound and/or CT scan and/or MRI, and bone scan. In cases of positive bone scans, bone X-ray evaluation was mandatory to rule out the possibility of metastatic bone scan positivity. Other tests may be performed as clinically indicated.
Negative pregnancy test (urine or serum) within 7 days prior to registration for all women of childbearing potential.
+1 more criteria

You may not qualify if:

Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
Prior anthracycline therapy, taxoids (paclitaxel, docetaxel) or platinum salts for any malignancy.
Prior radiation therapy for breast cancer.
Bilateral invasive breast cancer.
Pregnant, or lactating participants. Participants of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment (chemotherapy and tamoxifen therapy) and must had negative urine or serum pregnancy test within 7 days prior to registration.
Any T4 or N2 or known N3 or M1 breast cancer.
Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by National Cancer Institute (NCI) criteria.
Cardiac disease that would preclude the use of doxorubicin, docetaxel and Herceptin:
any documented myocardial infarction
angina pectoris that required the use of antianginal medication
any history of documented congestive heart failure
Grade 3 or Grade 4 cardiac arrhythmia (NCI Common Terminology Criteria \[CTC\], version 2.0)
clinically significant valvular heart disease
participants with cardiomegaly on chest x-ray or ventricular hypertrophy on ECG, unless they demonstrate by MUGA scan within the past 3 months that the LVEF was ≥ the lower limit of normal for the radiology facility;
participants with poorly controlled hypertension i.e. diastolic greater than 100 mm/Hg. (Participants who were well controlled on medication were eligible for entry)
+19 more criteria

Contact the study team to confirm eligibility.