Adjuvant Breast Cancer: Node positive or high risk node negative and HER 2 negative MedDRA version: 14.1 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Taxotere
Pharmaceutical Form: Solution for infusion
CAS Number: 148408-66-6
Other descriptive name: DOCETAXEL TRIHYDRATE
Concentration unit: mg/m2 milligram(s)/square meter
Concentration t
Sponsors
ICORG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -The patient must have signed and dated an approved consent form -Patients must be female. -patient must be = 18 and = 70 years old. - ECOG performance status of 0 or 1 (see Appendix B). - tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination. - HER2-negative breast cancer based on current ASCO/CAP Guideline Recommendations the following staging criteria must be met according to AJCC criteria: • By pathologic evaluation, ? primary tumor must be pT1-3; •, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b,pN1c), pN2a, pN3a, or pN3b If pN0, at least one of the following criteria must be met: - ER negative and PgR negative; or - Pathologic tumor size > 2.0 cm; or - T1c (pathologic tumor size > 1.0 cm but = 2.0 cm) and ER positive (PgR status may be positive or negative) and either grade 3 histology or Oncotype DX® Recurrence Score of = 25. -Patients must have undergone either a total mastectomy or breast-conserving surgery(lumpectomy) - For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist- For patients who undergo mastectomy, margins must be histologically free of invasive tumor and DCIS. -Patients must have completed one of the following procedures for evaluation of pathologic nodal status: • Sentinel lymphadenectomy alone if pathologic nodal staging based on sentinel lymphadenectomy is pN0, pN1mi, or pN1b; • Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive; or • Axillary lymphadenectomy without SN isolation procedure. -The interval between the last surgery for breast cancer (treatment or staging) and randomization must be at least 28 days but no more than 84 days. (-Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then PgR analysis must also be performed. (Either a core biopsy or surgical resection specimen can be used for ER/PgR testing.) -The most recent postoperative blood counts, performed within 6 weeks prior to randomization, must meet the following criteria: • ANC must be = 1200/mm3; • platelet count must be = 100,000/mm3; and • hemoglobin must be = 10 g/dL. -The following criteria for evidence of adequate hepatic function must be met based on the results of the most recent postoperative tests performed within 6 weeks prior to randomization: • total bilirubin must be = ULN for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin; and • alkaline phosphatase must be = 2.5 x ULN for the lab; and • AST must be = 1.5 x ULN for the lab. • Alkaline phosphatase and AST may not both be > the ULN. For example, if the alkaline phosphatase is > the ULN but = 2.5 x ULN, then the AST must be = the ULN. If the AST is > the ULN but = 1.5 x ULN, then the alkaline phosphatase must be = ULN. Note: If ALT is performed instead of AST (per institution's standard practice), the ALT value must be = 1.5 x ULN; if both were performed, the AST must be = 1.5 x ULN. NSABP B-46-I/USOR 07132 – Page 14 -Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan performed within 90 days prior to randomization) does not demonstrate metastatic disea
Exclusion criteria
Exclusion criteria: T4 tumors including inflammatory breast cancer. Definitive clinical or radiologic evidence of metastatic disease. (Chest imaging [mandatory for all patients] and other imaging within 90 days prior to randomization.) Synchronous or metachronous contralateral invasive breast cancer. (Patients with synchronous and/or metachronous contralateral DCIS are eligible.) Any history of ipsilateral invasive breast cancer or ipsilateral DCIS. History of non-breast malignancies within 5 years prior to randomization, except for the following: carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinomas of the skin. Previous therapy with anthracyclines, taxanes, or bevacizumab for any malignancy. Chemotherapy administered for the currently diagnosed breast cancer prior to randomization. Continued therapy with any hormonal agent such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor. (Patients are eligible if these medications are discontinued prior to randomization.) Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy Patients are eligible if these medications are discontinued prior to randomization. Known active hepatitis B or hepatitis C with abnormal liver function tests. Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. -Uncontrolled hypertension defined as systolic BP > 150 mmHg or diastolic BP > 90 mmHg, with or without anti-hypertensive medication. Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet eligibility requirements. History of hypertensive crisis or hypertensive encephalopathy. History of TIA or CVA. History of any arterial thrombotic event within 12 months prior to randomization. Symptomatic peripheral vascular disease. Intrinsic lung disease resulting in dyspnea. Unstable diabetes mellitus. Active infection or chronic infection requiring suppressive antibiotics. History of a major organ allograft or condition requiring chronic immunosuppression, e.g., kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases. (Patients who have received corneal transplants, cadaver skin, or bone transplants are eligible.) Any significant bleeding within 180 days prior to randomization, exclusive of menorrhagia in premenopausal women. Non-healing wound, skin ulcers, or incompletely healed bone fracture. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the planned start of study therapy. (Note: Placement of a vascular access device is not considered a major surgical procedure. See Section 7.3 for instructions regarding initiation of therapy after placement for Group 3 patients.) NSABP B-46-I/USOR 07132 – Page 16 Anticipation of need for major surgical procedures during study therapy and for at least 90 days following completion of bevacizumab. (See Section 7.9 regarding the timing of surgery to replace the tissue expanders with permanent implants for patients who have had breast reconstruction and other elective surgery.) Gastroduodenal ulcer(s) documented by endoscopy to be active within 180 days before randomization. History of GI perforation, abdominal fistulae, or intra-abdominal abscess. Known bleeding diathesis or coagulopathy. Requirement for therapeutic doses of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether the addition of Bevacizumab to the TC regimen (TCB) improves invasive disease-free survival (IDFS) relative to TC alone.;Secondary Objective: Invasive Dosease Free Survival-(IDFS):To determine whether the regimen of TCB improves IDFS relative to the TAC chemotherapy regimen. Disease Free Survival-(DFS-DCIS): To determine whether the regimen of TCB improves DFS-DCIS relative to the TAC regimen. Overall Survival-(OS): To determine whether the regimen of TCB improves OS relative to the TC alone regimen. To determine whether the regimen of TCB improves OS relative to the TAC regimen.;Primary end point(s): IDFS, defined as time to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence,invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colorectal carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer;Timepoint(s) of evaluation of this end point: It is estimated that it will take 32 months to accrue 3900 patients (1300 for each arm), and it will take another 34 months of follow-up to reach the required number of events to test the primary hypothesis. So, allowing an additional 6 months for data lock and report development, the total time to the initial release of findings will be about 6 years.There will be three interim analyses. The first interim analysis will take place at the first regularly scheduled meeting of the NSABP Data Safety Monitoring Committee (DSMC) after 95 events have occurred in total on the TCB + TC arms. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include IDFS for the comparison of TCB vs. TAC. Other secondary endpoints for the comparison of TCB vs. TC and TCB vs. TAC include disease-free survival (DFS-DCIS), overall survival (OS), and recurrence-free interval (RFI). DFS-DCIS is defined as time to local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy (invasive or non-invasive), regional recurrence, distant recurrence, contralateral breast cancer (invasive or non-invasive), second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colorectal carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. OS is defined as time from randomization until death from any cause. RFI is defined as time from randomization until local, regional, or distant recurrence.;Timepoint(s) of evaluation of this end point: No timepoints specified for secondary endpoints. | — |
Countries
Ireland
Contacts
Public ContactGroup Central Office
ICORG
Outcome results
None listed