BIG 02/98 Docetaxel - Breast Cancer

November 9, 2011 updated by: Sanofi

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.

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

2887

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Macquarie Park, Australia
        • Sanofi-Aventis
      • Vienna, Austria
        • Sanofi-Aventis
      • Diegem, Belgium
        • Sanofi-Aventis
      • Sao Paulo, Brazil, ao
        • Sanofi-Aventis
      • Providencia Santiago, Chile
        • Sanofi-Aventis
      • Praha, Czech Republic
        • Sanofi-Aventis
      • Horsholm, Denmark
        • Sanofi-Aventis
      • Berlin, Germany
        • Sanofi-Aventis
      • Budapest, Hungary
        • Sanofi-Aventis
      • Dublin, Ireland
        • Sanofi-Aventis
      • Natanya, Israel
        • Sanofi-Aventis
      • Milan, Italy
        • Sanofi-Aventis
      • Auckland, New Zealand
        • Sanofi-Aventis
      • Porto Salvo, Portugal
        • Sanofi-Aventis
      • Bratislava, Slovakia
        • Sanofi-Aventis
      • Ljubljana, Slovenia
        • Sanofi-Aventis
      • Gauteng, South Africa
        • Sanofi-Aventis
      • Barcelona, Spain
        • Sanofi-Aventis
      • Bromma, Sweden
        • Sanofi-Aventis
      • Geneve, Switzerland
        • Sanofi-Aventis
      • Guildford Surrey, United Kingdom
        • Sanofi-Aventis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: B
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
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.
ACTIVE_COMPARATOR: A1
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 810 events or median 5 year follow-up whichever occurs first
810 events or median 5 year follow-up whichever occurs first

Secondary Outcome Measures

Outcome Measure
Time Frame
DFS sequential/combined arms
Time Frame: 810 events or median 5 year follow-up whichever occurs first
810 events or median 5 year follow-up whichever occurs first
Safety NCI common toxicity criteria
Time Frame: from baseline to study end
from baseline to study end

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 1998

Primary Completion (ACTUAL)

September 1, 2011

Study Completion (ACTUAL)

September 1, 2011

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (ESTIMATE)

September 15, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

November 10, 2011

Last Update Submitted That Met QC Criteria

November 9, 2011

Last Verified

November 1, 2011

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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