None listed
Conditions
Brief summary
This project is investigating the optimal use of docetaxel and doxorubicin in the treatment of women with breast cancer and involved lymph nodes (N+). The efficacy of adjuvant chemotherapy in early breast cancer is well established by the international overview conducted by the Early Breast Cancer Trialist's Collaborative Group (EBCTCG). They have demonstrated the efficacy of adjuvant chemotherapy on reducing mortality and recurrence rates, but current regimens are far from optimal. Docetaxel (Taxotere), a new agent, has effectiveness and manageable side effects in the treatment of advanced breast cancer patients, and can plausibly improve outcomes for patients with early N+ breast cancer by optimal integration into current adjuvant chemotherapy regimens. This clinical trial is designed to compare whether it is advantageous to use docetaxel and/or doxorubicin in combination or sequentially with other currently available chemotherapy drugs
Interventions
Arm A1:doxorubicin 75 mg/m² i.v. once every 21 days for 4 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 24 weeks)
Arm A2:doxorubicin 60 mg/m² i.v. and cyclophosphamide 600 mg/m² i.v., once every 21 days for 4 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 4
Arm A1:doxorubicin 75 mg/m² i.v. once every 21 days for 4 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 24 weeks) Arm A2:doxorubicin 60 mg/m² i.v. and cyclophosphamide 600 mg/m² i.v., once every 21 days for 4 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 24 weeks) Arm B: doxorubicin 75 mg/m² i.v. day once every 21 days for 3 cycles, followed by Docetaxel 100 mg/m² i.v., once every 21 days for 3 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 30 weeks) Arm C: doxorubicin 50 mg/m² i.v. and docetaxel 75 mg/m² i.v. once every 21 days for 4 cycles, followed by CMF (C = Cyclophosphamide - 100 mg/m² orally for days 1-14, M = Methotrexate - 40 mg/m² i.v. on days 1 and 8, FU = Flourouracil - 600 mg/m² i.v. days 1 and 8, every 28 days) for 3 cycles. (total treatment duration is 24 weeks)
Sponsors
sanofi-aventis
Talavera Corporate Centre
Building D
12-24 Talavera Road
Macquarie Park, NSW 2113
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Written or witnessed informed consent. Histologically proven breast cancer. Definitive surgical treatment must be either mastectomy, or breast conserving surgery with axillary lymph node dissection. 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 eight resected lymph nodes. The determination of ER (estrogen receptor) and PgR (progesterone receptor) is mandatory. Karnofsky Performance status index > or equal to 70 %. Normal cardiac function must be confirmed by assessment of LVEF (MUGA scan or echocardiography). Laboratory requirements: (within 14 days prior to registration) a) Hematology: i) Neutrophils > or equal to 2.0 x 109/Lii) Platelets > or equal to 100 x 109/Liii) Hemoglobin > or equal to 10 g/dLb) Hepatic functioni) Total bilirubin < or equal to 1 x Upper Normal Limitii) ASAT (SGOT) and ALAT (SGPT) < or equal to 1.5 x Upper Normal Limitiii) Alkaline phosphatase < or equal to 2.5 x Upper Normal Limitc) Renal function:i) Creatinine < or equal to 150 µmol/L (1.5 mg/dL); Complete staging work-up within 3 months prior to registration, including bilateral mammography, chest Xray (PA and lateral) and/or CT-scan, abdominal ultrasound and/or CT scan, bone scan. Patients must be accessible for treatment and follow-up. 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 (chemo-hormono-immuno-therapy). 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 carcinoma. Patients with inoperable residual axillary nodal disease or with supraclavicular nodes.Pre-existing motor or sensory neurotoxicity of a severity > or equal to grade 2 by NCI criteria. Other serious illness or medical condition:o 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.o History of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.o Active uncontrolled infection.o Active peptic ulcer, unstable diabetes mellitus. Past or current history of other neoplasm except for:o Curatively treated basal cell skin cancer.o Adequately treated in situ carcinoma of the cervix. In regard to past or current history of other breast carcinoma, criteria of exclusion are:o Past history of ipsilateral or past/current history of contralateral invasive breast carcinoma.o 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 criteria of exclusion. Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (< or equal to 20 mg methylprednisolone or equivalent). Concurrent treatment with hormonal replacement therapy: this 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.
Outcome results
None listed