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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00174655




Registration number
NCT00174655
Ethics application status
Date submitted
9/09/2005
Date registered
15/09/2005
Date last updated
10/11/2011

Titles & IDs
Public title
BIG 02/98 Docetaxel - Breast Cancer
Scientific title
An Intergroup Phase III Trial to Evaluate the Activity of Docetaxel, Given Either Sequentially or in Combination With Doxorubicin, Followed by CMF, in Comparison to Doxorubicin Alone or in Combination With Cyclophosphamide, Followed by CMF, in the Adjuvant Treatment of Node-positive Breast Cancer Patients.
Secondary ID [1] 0 0
RP56976_PR_315
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Doxorubicine + docetaxel sequential
Treatment: Drugs - doxorubicine + cyclophosphamide sequential
Treatment: Drugs - doxorubicine + cyclophosphamide combined
Treatment: Drugs - doxorubicine + docetaxel combined

Active Comparator: A1 -

Active Comparator: A2 -

Experimental: B -

Experimental: C -


Treatment: Drugs: Doxorubicine + docetaxel sequential
doxorubicin 75 mg/m² i.v. day 1, q 21 days for 3 cycles, followed by docetaxel 100 mg/m² i.v., 1 hour infusion, day 1, q 21 days for 3 cycles, followed by CMF for 3 cycles

Treatment: Drugs: doxorubicine + cyclophosphamide sequential
doxorubicin 75 mg/m² i.v. day 1 q 21 days for 4 cycles, followed by CMF (C: cyclophosphamide 100 mg/m² orally days 1-14, M: methotrexate: 40 mg/m² i.v. days 1 and 8, FU; 5-fluorouracil: 600 mg/m²) i.v. days 1 and 8, q 28 days for 3 cycles

Treatment: Drugs: doxorubicine + cyclophosphamide combined
doxorubicin 60 mg/m² i.v. + cyclophosphamide 600 mg/m² i.v., day 1, q 21 days for 4 cycles, followed by CMF for 3 cycles.

Treatment: Drugs: doxorubicine + docetaxel combined
doxorubicin 50 mg/m² i.v. + docetaxel 75 mg/m² i.v. 1 hour infusion (1 hour after doxorubicin), day 1, q 21 days for 4 cycles, followed by CMF for 3 cycles.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DFS of docetaxel arms versus non toxanes arm (DFS: interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death for any cause whichever occurs first.
Timepoint [1] 0 0
810 events or median 5 year follow-up whichever occurs first
Secondary outcome [1] 0 0
DFS sequential/combined arms
Timepoint [1] 0 0
810 events or median 5 year follow-up whichever occurs first
Secondary outcome [2] 0 0
Safety NCI common toxicity criteria
Timepoint [2] 0 0
from baseline to study end

Eligibility
Key inclusion criteria
- Histologically proven breast cancer. Interval between definitive surgery that includes
axillary lymph node dissection and registration must be less than 60 days. A
representative sample of the primary tumor (either blocks or slides) must be sent to
the operational office, for central pathology reviews, after patients randomization.

- Definitive surgical treatment must be either mastectomy or breast conserving surgery,
with axillary lymph node dissection (not sampling) for operable breast cancer
(clinical T1-3, 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. Patients with
histologically-documented infiltration of the skin (pT4) will not be eligible.
Patients who have a breast conserving procedure with a positive margin may become
eligible if they subsequently undergo adequate resection or mastectomy with clear
margins.

- Histologic examination of the tumor: invasive adenocarcinoma with at least one
axillary lymph node (pN1) showing evidence of tumor among a minimum of eight resected
lymph nodes. All nodes must be examined by the pathologist. The determination of ER
(estrogen receptor) and PgR (progesterone receptor) is mandatory and results must be
known by the end of chemotherapy in order to decide whether hormonal therapy is
indicated (Biochemical or immunohistochemical methods required ; ER and/or PgR
positivity should be in accordance with the policy in use at each participating
center. Each center will specify its own policy).

- Age > or = 18 years and age < or = 70 years. The upper age limit is not meant to be
exclusionary but rather is based on the lack of safety data for women > 70 years of
age.

- Karnofsky Performance status index > or = 70 %.

- Normal cardiac function must be confirmed by LVEF (MUGA scan or echocardiography). The
result must be above the lower limit of normal for the institution.

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

- Hematology

- Neutrophils > or = 2.0 x 109/L

- Platelets > or =100 x 109/L

- Hemoglobin > or = 10 g/dL

- Hepatic function

- Total bilirubin < or = 1 UNL

- ASAT (SGOT) and ALAT (SGPT) < or = 1.5 UNL

- Alkaline phosphatase < or = 2.5 UNL

- Renal function

- Creatinine < or = 150 µmol/L (1.5 mg/dL)

- If creatinine is borderline, the calculated creatinine clearance should be >
or = 60 mL/min (Cockcroft formula).

- Complete staging work-up within 3 months prior to registration. All patients will have
bilateral mammography, chest X-ray (PA and lateral) and/or CT-scan, abdominal
ultrasound and/or CT scan, bone scan (in case of positive bone scan suspicious for
metastases, bone X-ray (or bone CT-scan for spine) on hot spots is mandatory to rule
out the possibility of metastatic hot spots). Other tests may be performed as
clinically indicated.

- Patients must be accessible for treatment and follow-up. Patients registered on this
trial must be treated and followed at a participating center which could be a
Principal or a co-investigator's site. In case patient moves during the follow-up,
every effort should be done to follow the patient in a participating center.

- Negative pregnancy test (urine or serum) within 7 days prior to registration for all
women of childbearing potential. Patients of childbearing potential must implement
adequate non-hormonal measures to avoid pregnancy during study treatment(chemotherapy,
radiotherapy and hormonal therapy).
Minimum age
18 Years
Maximum age
70 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior systemic anticancer therapy for breast cancer (chemo-immuno-hormonotherapy).

- Prior radiation therapy for breast cancer.

- Pregnant, or lactating patients.

- Any locally advanced (clinical or pathological T4 and/or N2-known N3) or
metastatic(M1) breast cancer.Patients with inoperable residual axillary nodal disease
or with supraclavicular nodes.

- Pre-existing motor or sensory neurotoxicity of a severity ³ grade 2 by NCI criteria.

- 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 other neoplasms except for:

- curatively treated basal cell skin cancer

- adequately treated in situ carcinoma of the cervix

- In regard to past or current history of other breast carcinoma, criteria of exclusion
are:

- past history of ipsilateral or past or current history of contralateral invasive
breast carcinoma

- past or current history of contralateral ductal in situ breast carcinoma

A past or current history of ipsilateral ductal in situ or lobular in situ (ipsilateral or
contralateral) breast carcinoma is not a criterion of exclusion.

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

- Concurrent treatment with 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.

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Austria
State/province [1] 0 0
Vienna
Country [2] 0 0
Belgium
State/province [2] 0 0
Diegem
Country [3] 0 0
Brazil
State/province [3] 0 0
Sao Paulo
Country [4] 0 0
Chile
State/province [4] 0 0
Providencia Santiago
Country [5] 0 0
Czech Republic
State/province [5] 0 0
Praha
Country [6] 0 0
Denmark
State/province [6] 0 0
Horsholm
Country [7] 0 0
Germany
State/province [7] 0 0
Berlin
Country [8] 0 0
Hungary
State/province [8] 0 0
Budapest
Country [9] 0 0
Ireland
State/province [9] 0 0
Dublin
Country [10] 0 0
Israel
State/province [10] 0 0
Natanya
Country [11] 0 0
Italy
State/province [11] 0 0
Milan
Country [12] 0 0
New Zealand
State/province [12] 0 0
Auckland
Country [13] 0 0
Portugal
State/province [13] 0 0
Porto Salvo
Country [14] 0 0
Slovakia
State/province [14] 0 0
Bratislava
Country [15] 0 0
Slovenia
State/province [15] 0 0
Ljubljana
Country [16] 0 0
South Africa
State/province [16] 0 0
Gauteng
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Sweden
State/province [18] 0 0
Bromma
Country [19] 0 0
Switzerland
State/province [19] 0 0
Geneve
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Guildford Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Primary objectives:

- To compare Disease-Free Survival (DFS) of an adjuvant treatment with docetaxel given
either sequentially or in combination with doxorubicin and followed by CMF to
doxorubicin alone or in combination with cyclophosphamide and followed by CMF in
operable breast cancer patients with positive axillary lymph nodes.

Secondary objectives:

- To compare DFS of an adjuvant treatment with doxorubicin followed by docetaxel followed
by CMF to doxorubicin followed by CMF in operable breast cancer patients with positive
axillary lymph nodes

- To compare DFS of an adjuvant treatment with docetaxel in combination with doxorubicin
followed by CMF to doxorubicin in combination with cyclophosphamide followed by CMF in
operable breast cancer patients with positive axillary lymph nodes

- To compare DFS of an adjuvant treatment with doxorubicin followed by docetaxel followed
by CMF to doxorubicin in combination with docetaxel followed by CMF in operable breast
cancer patients with positive axillary lymph nodes, (sequential mono-chemotherapy versus
polychemotherapy).

- To compare overall survival of treatment arms.

- To compare toxicity of treatment arms.

- To evaluate pathologic and molecular markers for predicting efficacy.

- Socioeconomic data will be collected in order to be able to perform a socioeconomic
analysis by country, when needed.
Trial website
https://clinicaltrials.gov/show/NCT00174655
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
Other publications