BIG 02/98 Docetaxel - Breast Cancer

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT00174655

Collaborator

(none)

2,887

Enrollment

Locations

Arms

159

Duration (Months)

137.5

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Doxorubicine + docetaxel sequential Drug: doxorubicine + cyclophosphamide sequential Drug: doxorubicine + cyclophosphamide combined Drug: doxorubicine + docetaxel combined	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

2887 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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.

Study Start Date :

Jun 1, 1998

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A1	Drug: 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
Active Comparator: A2	Drug: 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.
Experimental: B	Drug: 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
Experimental: C	Drug: 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.

Outcome Measures

Primary Outcome Measures

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. [810 events or median 5 year follow-up whichever occurs first]

Secondary Outcome Measures

DFS sequential/combined arms [810 events or median 5 year follow-up whichever occurs first]
Safety NCI common toxicity criteria [from baseline to study end]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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).

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Sanofi-Aventis	Macquarie Park	Australia
2	Sanofi-Aventis	Vienna	Austria
3	Sanofi-Aventis	Diegem	Belgium
4	Sanofi-Aventis	Sao Paulo	Brazil	ao
5	Sanofi-Aventis	Providencia Santiago	Chile
6	Sanofi-Aventis	Praha	Czech Republic
7	Sanofi-Aventis	Horsholm	Denmark
8	Sanofi-Aventis	Berlin	Germany
9	Sanofi-Aventis	Budapest	Hungary
10	Sanofi-Aventis	Dublin	Ireland
11	Sanofi-Aventis	Natanya	Israel
12	Sanofi-Aventis	Milan	Italy
13	Sanofi-Aventis	Auckland	New Zealand
14	Sanofi-Aventis	Porto Salvo	Portugal
15	Sanofi-Aventis	Bratislava	Slovakia
16	Sanofi-Aventis	Ljubljana	Slovenia
17	Sanofi-Aventis	Gauteng	South Africa
18	Sanofi-Aventis	Barcelona	Spain
19	Sanofi-Aventis	Bromma	Sweden
20	Sanofi-Aventis	Geneve	Switzerland
21	Sanofi-Aventis	Guildford Surrey	United Kingdom