FAC Versus FAC Plus Weekly Paclitaxel as Adjuvant Treatment of Node Negative High Risk Breast Cancer Patients
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Fluorouracil; Doxorubicin; Cyclophosphamide; Paclitaxel
Intervention description: Arm A: FAC Arm B: FAC-wP; Arm A: FAC Arm B: FAC-wP; Arm A: FAC Arm B: FAC-wP; Arm B: FAC-wP
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin; Fluorouracil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1925.0
Sex: Female
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Node negative, high risk breast cancer.; Prognostic gene profile.; Saint Gallen high risk criteria.; Weekly paclitaxel.

Summary:

      This is a prospective, open-label, randomized, phase III trial. Patients will be stratified
      after breast surgery, as per investigational site; menopausal status; node negative
      diagnosis, as per sentinel-node technique versus lymphadenectomy; hormone receptor status
      (positive versus negative).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent.

          -  Histological diagnoses of operable invasive adenocarcinoma of the breast (T1-T3).
             Tumors must be Human Epidermal Growth Factor Receptor 2 (HER2) negative. Patients must
             be free of disease in the axilla (node negative). If lymphadenectomy is done, at least
             10 nodes must be examined. If sentinel node technique is used, sentinel node must be
             free of disease. Patients must present at least one high risk criterion (St. Gallen,
             1998) as follows:

               -  Tumor size > 2 cm; and/or

               -  ER and Progesterone Receptor (PgR) negative; and/or

               -  Histological grade 2-3; and/or

               -  Age < 35 years old.

          -  Time window between surgery and study randomization must be less than 60 days.

          -  Surgery must consist of mastectomy or conservative surgery. Margins free of disease
             and ductal carcinoma in situ (DCIS) are required. Lobular carcinoma is not considered
             a positive margin.

          -  Patients must not present evidence of metastatic disease.

          -  Status of hormone receptors in primary tumor. Results must be available before the end
             of adjuvant chemotherapy.

          -  Status of HER2 in primary tumor, known before randomization. Patients with
             Immunohistochemistry (IHC) 0 or +1 are eligible. For patients with IHC 2+, fluorescent
             in situ hybridization (FISH) is mandatory and result must be negative.

          -  Age >= 18 and <= 70 years old.

          -  Performance status (Karnofsky index) >= 80.

          -  Normal electrocardiogram (EKG) in the 12 weeks prior to randomization. If needed,
             normal cardiac function must be confirmed by left ventricular ejection fraction
             (LVEF).

          -  Laboratory results (within 14 days prior to randomization):

               -  Hematology: neutrophils >= 1.5 x 10^9/l; platelets >= 100x 10^9/l; hemoglobin >=
                  10 mg/dl;

               -  Hepatic function: total bilirubin <= 1 upper normal limit (UNL); Aspartate
                  aminotransferase (AST) and Alanine aminotransferase (ALT) <= 2.5 UNL; alkaline
                  phosphatase <= 2.5 UNL. If values of AST and ALT > 1.5 UNL are associated with
                  alkaline phosphatase > 2.5 UNL, patient is not eligible.

               -  Renal function: creatinine <= 175 mmol/l (2 mg/dl); creatinine clearance >= 60
                  ml/min.

          -  Complete stage workup during the 12 weeks prior to randomization (mammograms are
             allowed within a 20 week time window). All patients must have a bilateral mammogram,
             thorax x-ray, abdominal echography and/or computed tomography (CT)-scan. If bone pain,
             and/or alkaline phosphatase elevation, a bone scintigraphy is mandatory. This test is
             recommended for all patients. Other tests, as clinically indicated.

          -  Patients able to comply with treatment and study follow-up.

          -  Negative pregnancy test done in the 14 previous days to randomization.

        Exclusion Criteria:

          -  Prior systemic therapy for breast cancer.

          -  Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any
             malignancy.

          -  Prior radiotherapy for breast cancer.

          -  Bilateral invasive breast cancer.

          -  Pregnant or lactating women. Adequate contraceptive methods must be used during
             chemotherapy and hormone therapy treatments. Negative pregnancy test in the 14
             previous days to randomization.

          -  Any T4 or N1-3 or M1 tumor.

          -  HER2 positive breast cancer (IHC 3+ or positive FISH result).

          -  Pre-existing grade >=2 motor or sensorial neurotoxicity by the National Cancer
             Institute Common Toxicity Criteria (NCICTC) v-2.0.

          -  Any other serious medical pathology, such as congestive heart failure, unstable
             angina, history of myocardial infarction during the previous year, uncontrolled
             hypertension or high risk arrhythmias.

          -  History of neurological or psychiatric disorders, which could preclude the patients to
             free informed consent.

          -  Active uncontrolled infection.

          -  Active peptic ulcer; unstable diabetes mellitus.

          -  Previous or current history of neoplasms different from breast cancer, except for skin
             carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and
             without recurrence in the last 10 years; ductal in situ carcinoma in the same breast;
             lobular in situ carcinoma.

          -  Concomitant treatment with other investigational products. Participation in other
             clinical trials with a non-marketed drug in the 20 previous days before randomization.

          -  Concomitant treatment with other therapy for cancer.

          -  Males.