Docetaxel in Breast Cancer

Overview[ - collapse ][ - ]

Purpose 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.
ConditionBreast Cancer
InterventionDrug: docetaxel, doxorubicin, cyclophosphamide
Drug: Docetaxel,doxorubicin, cyclophosphamide
PhasePhase 3
SponsorSanofi
Responsible PartySanofi
ClinicalTrials.gov IdentifierNCT00312208
First ReceivedApril 5, 2006
Last UpdatedDecember 4, 2013
Last verifiedDecember 2013

Tracking Information[ + expand ][ + ]

First Received DateApril 5, 2006
Last Updated DateDecember 4, 2013
Start DateNovember 2001
Estimated Primary Completion DateOctober 2013
Current Primary Outcome MeasuresLocal, Regional or Metastatic Relapse, or Second Primary Cancer, or Death From Any Cause (Disease-Free Survival) [Time Frame: Median follow-up 65 months] [Designated as safety issue: No]The primary event is the local, regional or metastatic relapse or the date of second primary cancer or death from any cause (whichever occurs first). The primary efficacy analysis is performed on the time from randomization to this primary event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
Current Secondary Outcome MeasuresDeath From Any Cause (Overall Survival) [Time Frame: Median follow-up of 65 months] [Designated as safety issue: No]The considered event is death from any cause. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.

Descriptive Information[ + expand ][ + ]

Brief TitleDocetaxel in Breast Cancer
Official TitleA 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
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionBreast Cancer
InterventionDrug: 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.
Drug: 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.
Study Arm (s)
  • Experimental: 1
    Doxorubicin in combination with cyclophosphamide followed by docetaxel (AC -> T)
  • Experimental: 2
    Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment3299
Estimated Completion DateOctober 2013
Estimated Primary Completion DateOctober 2008
Eligibility 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.

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.
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Argentina, Australia, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, China, Colombia, Croatia, Cyprus, Czech Republic, Egypt, Estonia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Korea, Republic of, Lebanon, Mexico, New Zealand, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Slovenia, South Africa, Spain, Taiwan, Uruguay, Venezuela

Administrative Information[ + expand ][ + ]

NCT Number NCT00312208
Other Study ID NumbersTAX_GMA_301
Has Data Monitoring CommitteeNot Provided
Information Provided BySanofi
Study SponsorSanofi
CollaboratorsCancer International Research Group
Investigators Study Director: Jean-Philippe AUSSEL Sanofi
Verification DateDecember 2013

Locations[ + expand ][ + ]

Sanofi-Aventis
Bridgewater, New Jersey, United States, 08807
Sanofi-Aventis
Buenos Aires, Argentina
Sanofi-Aventis
Macquarie Park, Australia
Sanofi-Aventis
Brussels, Belgium
Sanofi-Aventis
Sarajevo, Bosnia and Herzegovina
Sanofi-Aventis
Sao Paulo, Brazil
Sanofi-Aventis
Sofia, Bulgaria
Sanofi-Aventis
Laval, Canada
Sanofi-Aventis
Shanghai, China
Sanofi-Aventis
Bogota, Colombia
Sanofi-Aventis
Zagreb, Croatia
Sanofi-Aventis
Nikosia, Cyprus
Sanofi-Aventis
Praha, Czech Republic
Sanofi-Aventis
Cairo, Egypt
Sanofi-Aventis
Tallin, Estonia
Sanofi-Aventis
Paris, France
Sanofi-Aventis
Berlin, Germany
Sanofi-Aventis
Kallithea, Greece
Sanofi-Aventis
Hong Kong, Hong Kong
Sanofi-Aventis
Budapest, Hungary
Sanofi-Aventis
Dublin, Ireland
Sanofi-Aventis
Natanya, Israel
Sanofi-Aventis
Seoul, Korea, Republic of
Sanofi-Aventis
Beirut, Lebanon
Sanofi-Aventis
Mexico, Mexico
Sanofi-aventis
Auckland, New Zealand
Sanofi-Aventis
Warsaw, Poland
Sanofi-Aventis
Porto Salvo, Portugal
Sanofi-Aventis
Bucuresti, Romania
Sanofi-Aventis
Moscow, Russian Federation
Sanofi-Aventis
Jeddah, Saudi Arabia
Sanofi-Aventis
Ljubljana, Slovenia
Sanofi-Aventis
Midrand, South Africa
Sanofi-Aventis
Barcelona, Spain
Sanofi-Aventis
Taipei, Taiwan
Sanofi-Aventis
Montevideo, Uruguay
Sanofi-Aventis
Caracas, Venezuela