A Phase III Clinical Trial Comparing Docetaxol and Cyclophosphamide (known as the TC chemotherapy regimen) to Doxorubicin, Cyclophosphamide and Docetaxol (known as the TAC chemotherapy regimen) for Women with Node-Positive orHigh-Risk Node-Negative, HER2-Negative Breast Cancer

Phase 1

• Conditions: Adjuvant Breast Cancer: Node positive or high risk node negative and HER 2 negative; MedDRA version: 14.1Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-021587-15-IE
• Lead Sponsor: ICORG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-08
• Last Update Posted: 28 May 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 140

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified