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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00312208




Registration number
NCT00312208
Ethics application status
Date submitted
5/04/2006
Date registered
7/04/2006
Date last updated
30/12/2013

Titles & IDs
Public title
Docetaxel in Breast Cancer
Scientific title
A Multicenter Phase III Randomized Trial Comparing Docetaxel in Combination With Doxorubicin and Cyclophosphamide Versus Doxorubicin and Cyclophosphamide Followed by Docetaxel as Adjuvant Treatment of Operable Breast Cancer HER2neu Negative Patients With Positive Axillary Lymph Nodes
Secondary ID [1] 0 0
BCIRG 005
Secondary ID [2] 0 0
TAX_GMA_301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - docetaxel, doxorubicin, cyclophosphamide
Treatment: Drugs - Docetaxel,doxorubicin, cyclophosphamide

Experimental: 1 - Doxorubicin in combination with cyclophosphamide followed by docetaxel (AC -> T)

Experimental: 2 - Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)


Treatment: Drugs: docetaxel, doxorubicin, cyclophosphamide
TAC x 6 : Docetaxel 75 mg/m² as 1 hour IV infusion on day 1 every 3 weeks in combination with doxorubicin 50 mg/m² as an IV bolus and cyclophosphamide 500 mg/m2 as IV on day 1 every 3 weeks. Sequence of administration is as follows: doxorubicin followed by cyclophosphamide followed by docetaxel.

Treatment: Drugs: Docetaxel,doxorubicin, cyclophosphamide
AC x 4: Doxorubicin 60 mg/m² as an IV bolus in combination with cyclophosphamide 600 mg/m² as IV followed by docetaxel 100 mg/m² as 1 hour IV infusion on day 1 every 3 weeks for 4 cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Local, Regional or Metastatic Relapse, or Second Primary Cancer, or Death From Any Cause (Disease-Free Survival)
Timepoint [1] 0 0
Median follow-up 65 months
Secondary outcome [1] 0 0
Death From Any Cause (Overall Survival)
Timepoint [1] 0 0
Median follow-up of 65 months

Eligibility
Key inclusion criteria
Inclusion Criteria :

- Histologically proven breast cancer. Interval between definitive surgery that includes
axillary lymph node dissection and registration is less than or equal to 60 days. A
central pathology review may be performed post randomization for confirmation of
diagnosis and molecular studies.

- Definitive surgical treatment must be either mastectomy, or breast conserving surgery
with axillary lymph node dissection 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 Ductal Carcinoma In Situ (DCIS). Lobular carcinoma
in-situ does not count as a positive margin.

- Histologic examination of the tumor: Invasive adenocarcinoma with at least one
axillary lymph node (pN1) showing evidence of tumor among a minimum of six resected
lymph nodes.

- Tumor must show negative HER2 neu proto-oncogene overexpression by FISH (Fluorescence
In Situ Hybridization). Confirmation of non overexpression will be centrally assessed
by authorized BCIRG (Breast Cancer International Research Group) laboratories prior to
randomization.

- Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to
randomization. Results must be known at the time of randomization.(Note: Patients
whose tumor is estrogen receptor negative with progesterone receptor status unknown or
undetermined, must have the progesterone receptor assayed in order to determine
hormonal receptor status. Patients whose tumor is progesterone receptor negative with
estrogen receptor status unknown or undetermined, must have the estrogen receptor
assayed in order to determine hormonal receptor status).

- Karnofsky Performance status index > 80%.

- Normal cardiac function must be confirmed by LVEF (Lef Ventricular Ejection Fraction)
i.e. MUGA (Multi Gated Acquisition) scan or echocardiography and ECG within 3 months
prior to registration. LVEF result must be above or equal to the lower limit of normal
for the institution. The ECG results must be within normal limits or show no
significant abnormalities.

- Laboratory requirements: (within 14 days prior to registration)

- Hematology:

- Neutrophils > or = 2.0 x 10^9/L

- Platelets > or = 100 x 10^9/L

- Hemoglobin > or = 10 g/dL

- Hepatic function:

- Total bilirubin < or = 1 UNL (Upper Normal Limit)

- ASAT (Aspartate Amino Transferase) and ALAT (Alanine Amino Transferase) < or
= 2.5 UNL

- Alkaline phosphatase < or = 5 UNL

- Patients with ASAT and/or ALAT > 1.5 x UNL associated with alkaline
phosphatase > 2.5 x UNL are not eligible for the study.

- Renal function:

- Creatinine < or = 175 µmol/L (2 mg/dL);

- If limit reached, the calculated creatinine clearance should be > or =
60mL/min.

- Complete staging work-up within 3 months prior to registration. All patients will have
contralateral mammography, chest X-ray (Posteroanterior and lateral) and/or CT scan
and/or MRI (Magnetic Resonance Imaging), abdominal ultrasound and/or CT scan
(computerized tomography) and/or MRI, and bone scan. In case of positive bone scan,
bone X-ray is mandatory to rule out the possibility of non-metastatic hot spots. 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.
Minimum age
18 Years
Maximum age
70 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria :

- Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy,
genetherapy , chemotherapy).

- Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy.

- Prior radiation therapy for breast cancer.

- Bilateral invasive breast cancer.

- Pregnant, or lactating patients. Patients of childbearing potential must implement
adequate non-hormonal contraceptive measures during study treatment (chemotherapy and
tamoxifen therapy) and must have 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 NCI-CTC
(National Cancer Institute - Common Toxicity Criteria), version 2.0.

- Other serious illness or medical condition:

- congestive heart failure or unstable angina pectoris, previous history of
myocardial infarction within 1 year from study entry, uncontrolled hypertension
or high-risk uncontrolled arrhythmias

- history of significant neurologic or psychiatric disorders including psychotic
disorders, dementia or seizures that would prohibit the understanding and giving
of informed consent

- active uncontrolled infection

- active peptic ulcer, unstable diabetes mellitus

- Past or current history of neoplasm other than breast carcinoma, except for:

- curatively treated non-melanoma skin cancer

- carcinoma in situ of the cervix

- other cancer curatively treated and with no evidence of disease for at least 10
years

- ipsilateral ductal carcinoma in-situ (DCIS) of the breast

- lobular carcinoma in-situ (LCIS) of the breast

- Chronic treatment with corticosteroids unless initiated > 6 months prior to study
entry and at low dose (< 20 mg methylprednisolone or equivalent).

- Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment should
be stopped before study entry.

- Definite contraindications for the use of corticosteroids.

- Concurrent treatment with other experimental drugs. Participation in another clinical
trial with any investigational not marketed drug within 30 days prior to study entry.

- Concurrent treatment with any other anti-cancer therapy.

- Current therapy with any hormonal agent such as raloxifene, tamoxifen or other
selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention.
Patients must have discontinued these agents prior to randomization.

The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2001
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2013
Sample size
Target
Accrual to date
Final
3299
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis - Macquarie Park
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Belgium
State/province [3] 0 0
Brussels
Country [4] 0 0
Bosnia and Herzegovina
State/province [4] 0 0
Sarajevo
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Sofia
Country [7] 0 0
Canada
State/province [7] 0 0
Laval
Country [8] 0 0
China
State/province [8] 0 0
Shanghai
Country [9] 0 0
Colombia
State/province [9] 0 0
Bogota
Country [10] 0 0
Croatia
State/province [10] 0 0
Zagreb
Country [11] 0 0
Cyprus
State/province [11] 0 0
Nikosia
Country [12] 0 0
Czech Republic
State/province [12] 0 0
Praha
Country [13] 0 0
Egypt
State/province [13] 0 0
Cairo
Country [14] 0 0
Estonia
State/province [14] 0 0
Tallin
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Greece
State/province [17] 0 0
Kallithea
Country [18] 0 0
Hong Kong
State/province [18] 0 0
Hong Kong
Country [19] 0 0
Hungary
State/province [19] 0 0
Budapest
Country [20] 0 0
Ireland
State/province [20] 0 0
Dublin
Country [21] 0 0
Israel
State/province [21] 0 0
Natanya
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Lebanon
State/province [23] 0 0
Beirut
Country [24] 0 0
Mexico
State/province [24] 0 0
Mexico
Country [25] 0 0
New Zealand
State/province [25] 0 0
Auckland
Country [26] 0 0
Poland
State/province [26] 0 0
Warsaw
Country [27] 0 0
Portugal
State/province [27] 0 0
Porto Salvo
Country [28] 0 0
Romania
State/province [28] 0 0
Bucuresti
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Moscow
Country [30] 0 0
Saudi Arabia
State/province [30] 0 0
Jeddah
Country [31] 0 0
Slovenia
State/province [31] 0 0
Ljubljana
Country [32] 0 0
South Africa
State/province [32] 0 0
Midrand
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taipei
Country [35] 0 0
Uruguay
State/province [35] 0 0
Montevideo
Country [36] 0 0
Venezuela
State/province [36] 0 0
Caracas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cancer International Research Group (CIRG)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Primary objective :

- To compare disease-free survival after treatment with docetaxel in combination with
doxorubicin and cyclophosphamide to doxorubicin and cyclophosphamide followed by
docetaxel in operable adjuvant breast cancer HER2neu negative patients with positive
axillary lymph nodes.

Secondary objectives :

- To compare toxicity and quality of life between the 2 above-mentioned arms.

- To evaluate pathologic and molecular markers for predicting efficacy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00312208
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jean-Philippe AUSSEL
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00312208