EC Followed Docetaxel Versus ET Followed Capecitabine as Adjuvant Chemotherapy for Node Positive Operable Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Docetaxel; Capecitabine; Epirubicin; Cyclophosphamide
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Capecitabine; Epirubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1384.0
Sex: Female
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: HER2 negative breast cancer; Node positive breast cancer; Adjuvant treatment; Oral chemotherapy

Summary:

      This is a prospective, randomised phase III trial, to compare the efficacy and safety
      profiles of two types of adjuvant chemotherapy regimens for human epidermal growth factor
      receptor 2 (HER2) negative, node positive breast cancer patients.

      Control Arm: This includes 4 cycles of EC 90/600 mg/m2 day 1 every 3 weeks, followed by 4
      cycles of T 100 mg/m2 day 1 every 3 weeks.

      Experimental Arm: This includes 4 cycles of ET 90/75 mg/m2, day 1 every 3 weeks, followed by
      4 cycles of capecitabine 1250 mg/m2, twice a day, via oral intake, for 14 days, and then a
      one-week rest period.

      Premenopausal women with hormone receptor positive tumours must receive 5 years of tamoxifen
      after the end of chemotherapy.

      Postmenopausal women with hormone receptor positive tumours can receive tamoxifen or
      aromatase inhibitors (or both) after the end of chemotherapy.

      Patients may receive radiotherapy when clinically indicated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent.

          -  Histological diagnosis of operable invasive adenocarcinoma of the breast (T1-T3).
             Tumours must be HER2 negative. Time window between surgery and study randomization
             must be less than 60 days.

          -  Surgery must consist of mastectomy or conservative surgery with axillary lymph node
             dissection. Margins free of disease and ductal carcinomas in situ (DCIS) are required.
             Lobular carcinoma is not considered a positive margin.

          -  Positive axillary lymph nodes defined as at least 1 out of 10 nodes with presence of
             disease. If sentinel node technique is used, sentinel node can be the only node
             affected. Patients belonging to the following classifications are eligible: TNM
             pathologic stage N1a, TNM pathologic stage N2a, TNM pathologic stage N3a.

          -  Status of hormone receptors in primary tumour. Results must be available before the
             end of adjuvant chemotherapy.

          -  Patients must not present evidence of metastatic disease. Status of HER2 in primary
             tumour, known before randomization. Patients with immune histochemistry (IHC) 0 or +1
             are eligible. For patients with IHC 2+, fluorescence 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 >= 100 x 10^9/l; hemoglobin >=
                  10 mg/dl;

               -  Hepatic function: total bilirubin <= 1 upper normal limit (UNL); serum
                  glutamic-oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase
                  (SGPT) <= 2.5 UNL; alkaline phosphatase <= 2.5 UNL. If values of SGOT and SGPT >
                  1.5 UNL are associated to alkaline phosphatase > 2.5 UNL, patient is not
                  eligible;

               -  Renal function: creatinine <= 175 mmol/l (2 mg/dl); creatinine clearance >= 60
                  ml/min;

               -  Pharmacogenetics: one blood sample is needed for single nucleotide polymorphism
                  (SNP) assessment.

          -  Complete stage workup during the 12 weeks prior to randomization (mammograms are
             allowed within a 20 week 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 prior 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.

          -  Any T4 or M1 tumour.

          -  Axillary lymph nodes: patients belonging to the following classifications are
             excluded: TNM pathologic stage N1b, TNM pathologic stage N1c, TNM pathologic stage
             N2b, TNM pathologic stage N3b, TNM pathologic stage N3c.

          -  HER2 positive breast cancer (IHC 3+ or positive FISH result).

          -  Pre-existing grade >= 2 motor or sensorial neurotoxicity (National Cancer Institute
             Common Toxicity Criteria version 2.0 [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
             from 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 tumour curatively treated and
             without recurrence in the last 10 years; ductal in situ carcinoma in the same breast;
             lobular in situ carcinoma.

          -  Chronic treatment with corticosteroids.

          -  Contraindications for corticosteroid administration.

          -  Concomitant treatment with raloxifene, tamoxifen or other selective estrogen receptor
             modulators (SERMs), either for osteoporosis treatment or for prevention. These
             treatments must stop before randomisation.

          -  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 another therapy for cancer.

          -  Males.