Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel With or Without Carboplatin in Treating Patients With Triple-Negative Breast Cancer

Not Recruiting

Trial ID: NCT02488967

Purpose

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.

Official Title

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

Stanford Investigator(s)

Irene Wapnir, MD
Irene Wapnir, MD

Professor of Surgery (General Surgery)

Melinda L. Telli, M.D.
Melinda L. Telli, M.D.

Professor of Medicine (Oncology)

Eligibility


Inclusion Criteria:

   - The patient must have signed and dated an institutional review board (IRB)-approved
   consent form that conforms to federal and institutional guidelines

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

   - The tumor must be unilateral invasive adenocarcinoma of the breast on histologic
   examination

   - All of the following staging criteria (according to the 7th edition of the American
   Joint Committee on Cancer [AJCC] Cancer Staging Manual) must be met:

      - By pathologic evaluation, primary tumor must be pT1-3

      - By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b,
      pN1c), pN2a, pN2b, pN3a, or pN3b

      - If pN0, pathological tumor must be greater than or equal to 3.0 cm

   - 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) less than 2.0, and if reported, average
      HER2 gene copy number less than 4 signals/cells; or

      - ISH non-amplified with a ratio of HER2 to CEP17 less than 2.0, and if reported,
      average HER2 gene copy number less than 4 signals/cells

   - The tumor must have estrogen receptor (ER)-and progesterone receptor (PgR)-status
   assessed using current American Society of Clinical Oncology (ASCO)/College of
   American Pathologists (CAP) guidelines; patients are eligible if the tumor staining
   meets one of the following criteria:

   - ER-negative and PgR-negative by ASCO/CAP guidelines, OR

   - ER or PgR stains are positive in 1-9% of cells and neither is positive in greater than
   or equal to 10% of cells.

   - The patient must have undergone either a mastectomy (total, skin-sparing, or
   nipple-sparing) or lumpectomy

   - For patients who undergo lumpectomy, the margins of the resected specimen must be
   histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as
   determined by the local pathologist; if pathologic examination demonstrates tumor at
   the line of resection, additional excisions may be performed to obtain clear margins;
   if tumor is still present at the resected margin after re-excision(s), the patient
   must undergo mastectomy to be eligible; (patients with margins positive for lobular
   carcinoma in situ [LCIS] are eligible without additional resection)

   - For patients who undergo mastectomy, the margins must be free of residual gross tumor;
   (patients with microscopic positive margins are eligible as long as post-mastectomy
   radiation therapy [RT] of the chest wall will be administered)

   - The patient must have completed one of the procedures for evaluation of pathologic
   nodal status listed below.

      - Sentinel lymphadenectomy alone:

         - If pathologic nodal staging based on sentinel lymphadenectomy is pN0 or
         pN1b;

         - If pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or
         pN1a and the patient has undergone breast conserving surgery (with planned
         breast radiotherapy), the primary tumor must be T1 or T2 by pathologic
         evaluation and the nodal involvement must be limited to 1 or 2 positive
         nodes

      - 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

   - Absolute neutrophil count (ANC) must be greater than or equal to1200/mm^3

   - Platelet count must be greater than or equal 100,000/mm^3

   - Hemoglobin must be greater than or equal to 10 g/dL

   - Adequate hepatic function must be met based on the results of the most recent
   postoperative tests performed with 6 weeks prior to randomization.

   - Total bilirubin must be less than or equal to upper limit of normal (ULN) for the
   laboratory (lab) unless the patient has a bilirubin elevation greater than ULN to 1.5
   x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of
   bilirubin

   - Alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab

   - Aspartate aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab

      - Note: If alanine aminotransferase (ALT) is performed instead of AST (per
      institution's standard practice), the ALT value must be less than or equal to 1.5
      x ULN; if both were performed, the AST must be less than or equal to 1.5 x ULN.

   - Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion
   in the study if liver imaging (computed tomography [CT], magnetic resonance imaging
   [MRI], positron emission tomography [PET]-CT, or PET scan) performed within 90 days
   prior to randomization does not demonstrate metastatic disease and the requirements
   above are met

   - Patients with alkaline phosphatase that is greater than ULN but less than or equal to
   2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone
   scan, PET-CT scan, or PET scan performed within 90 days prior to randomization does
   not demonstrate metastatic disease

   - Adequate renal function determined within 6 weeks prior to randomization defined as
   the most recent serum creatinine less than or equal to ULN or measured or calculated
   creatinine clearance greater than 60 mL/min

   - Left ventricular ejection fraction (LVEF) assessment must be performed within 90 days
   prior to randomization; (LVEF assessment performed by 2-dimensional [D] echocardiogram
   is preferred; however, multi gated acquisition [MUGA] scan may be substituted based on
   institutional preferences;) the LVEF must be greater than or equal to 50% regardless
   of the cardiac imaging facility's lower limit of normal.

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; this includes but is not confined to:

      - Active cardiac disease

         - Angina pectoris that requires the current use of anti-anginal medication;

         - Ventricular arrhythmias except for benign premature ventricular
         contractions;

         - Supraventricular and nodal arrhythmias requiring a pacemaker or not
         controlled with medication;

         - Conduction abnormality requiring a pacemaker;

         - Valvular disease with documented compromise in cardiac function; or

         - Symptomatic pericarditis

      - History of cardiac disease

         - Myocardial infarction documented by elevated cardiac enzymes or persistent
         regional wall abnormalities on assessment of left ventricle (LV) function;

         - History of documented congestive heart failure (CHF); or

         - Documented cardiomyopathy

   - Uncontrolled hypertension defined as sustained systolic blood pressure (BP) greater
   than 150 mmHg or diastolic BP greater than 90 mmHg; (patients with initial BP
   elevations are eligible if initiation or adjustment of BP medication lowers pressure
   to meet entry criteria)

   - Active hepatitis B or hepatitis C with abnormal liver function tests

   - Patients known to be human immunodeficiency virus (HIV) positive with a baseline
   cluster of differentiation (CD)4 count of less than 250 cells/mm^3 or have a history
   of acquired immune deficiency syndrome (AIDS) indicator conditions

   - Intrinsic lung disease resulting in dyspnea

   - History of hospitalization in past 12 months for diabetic ketoacidosis (DKA) or
   hyperosmolar hyperglycemic nonketotic syndrome (HHNS)

   - Active infection or chronic infection requiring chronic suppressive antibiotics

   - Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral
   sensory neuropathy) greater than or equal to grade 2, per the Common Terminology
   Criteria for Adverse Events (CTCAE) version (v)4.0

   - Conditions that would prohibit administration of corticosteroids

   - Chronic daily treatment with corticosteroids with a dose of greater than or equal to
   10 mg/day methylprednisolone equivalent (excluding inhaled steroids)

   - Known hypersensitivity to any of the study drugs or excipients, e.g., polysorbate 80
   and Cremophor® EL

   - Other non-malignant systemic disease that would preclude the patient from receiving
   study treatment or would prevent required follow-up

   - Psychiatric or addictive disorders or other conditions that, in the opinion of the
   investigator, would preclude the patient from meeting the study requirements

   - Pregnancy or lactation at the time of study entry; (note: pregnancy testing according
   to institutional standards for women of childbearing potential must be performed
   within 2 weeks prior to randomization)

   - Use of any investigational product within 4 weeks prior to randomization

Intervention(s):

drug: Carboplatin

drug: Cyclophosphamide

drug: Doxorubicin Hydrochloride

other: Laboratory Biomarker Analysis

drug: Paclitaxel

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Kathryn Bucknell
650-723-0659

Stanford Cancer Center South Bay
2589 Samaritan Drive
San Jose, CA 95124
Ann Moffat
650 721-4096

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