A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel with or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer

This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in treating patients with triple-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether doxorubicin hydrochloride and cyclophosphamide is more effective when followed by paclitaxel alone or paclitaxel and carboplatin in treating triple-negative breast cancer.

Inclusion Criteria:
• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination
• The tumor must have been determined to be human epidermal growth factor receptor 2 (HER2)-negative as follows:
-Immunohistochemistry (IHC) 0-1+; or
-IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to centromere enumerator probe 17 (CEP17) < 2.0; or
-ISH non-amplified with a ratio of HER2 to CEP17 < 2.0
• The tumor must have been determined to be estrogen receptor (ER)-and progesterone receptor (PgR)-negative
• The patient must have undergone either a mastectomy (total, skin-sparing, or nipple-sparing) or lumpectomy
• The patient must have completed one of the procedures for evaluation of pathologic nodal status listed below.
-Sentinel lymphadenectomy alone; or
-Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive; or
-Axillary lymphadenectomy with or without SN isolation procedure
• The interval between the last surgery for breast cancer (including re-excision of margins) and randomization must be no more than 60 days

Exclusion Criteria:
• T4 tumors including inflammatory breast cancer
• Definitive clinical or radiologic evidence of metastatic disease; required imaging studies must have been performed within 90 days prior to randomization
• Synchronous or previous contralateral invasive breast cancer; (patients with synchronous and/or previous contralateral DCIS or LCIS are eligible)
• Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS; (patients with synchronous or previous ipsilateral LCIS are eligible)
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization
• Previous therapy with anthracyclines or taxanes for any malignancy
• Chemotherapy administered for the currently diagnosed breast cancer prior to randomization
• Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy; patients are eligible if these medications are discontinued prior to randomization
• 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 sustained systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg
• Intrinsic lung disease resulting in dyspnea
• History of hospitalization in past 12 months for diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic nonketotic syndrome (HHNS)
• Chronic daily treatment with corticosteroids with a dose of >= 10 mg/day methylprednisolone equivalent (excluding inhaled steroids)
Phase III
Dan Zuckerman, M.D.
NRG (NRG Oncology)
Nikki Moxon

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.