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Neoadjuvant Treatment of Triple Negative Breast Cancer Patients with Docetaxel and Carboplatin to Assess Anti-tumor Activity

Trial Status: Active

This phase II trial studies how well docetaxel and carboplatin before surgery works in treating patients with stage II-III triple-negative breast cancer that has not previously been treated. Drugs used in chemotherapy, such as docetaxel 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. Giving docetaxel and carboplatin before surgery may help increase the number of patients with no evidence of cancer left after their treatment.

Inclusion Criteria

  • Newly diagnosed American Joint Committee on Cancer (AJCC)7 clinical stage II or III breast cancer with complete surgical excision of the breast cancer after neoadjuvant chemotherapy as the treatment goal
  • Patients with progesterone receptor positive (PR+) tumors are allowed
  • Human epidermal growth factor receptor 2 (HER2) negative by fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
  • Estrogen receptor (ER) less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor
  • Tumor size at least 2 cm in one dimension by clinical or radiographic exam (World Health Organization [WHO] criteria); patients with palpable lymph nodes may be enrolled regardless of tumor size
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcl
  • Platelets >= 100,000/mcl
  • Serum bilirubin within (or under) normal limits (OR total bilirubin =< 3.0 x institutional upper limit of normal [IULN] with direct bilirubin within normal range in patients with well documented Gilbert syndrome)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) within (or under) normal limits
  • Creatinine clearance >= 30 mL/min/1.73 m^2
  • Patients may be pre- or post-menopausal; women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)
  • Able to tolerate PET/magnetic resonance imaging (MRI) with intravenous contrast administration and must complete the applicable MRI screening evaluation form

Exclusion Criteria

  • Prior systemic therapy for the indexed breast cancer
  • A history of other malignancy =< 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix
  • Patients with bilateral or inflammatory breast cancer
  • Currently receiving any other investigational agents
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or carboplatin
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and/or breastfeeding; patient must have a negative serum pregnancy test within 7 days of study entry if premenopausal
  • Known human immunodeficiency virus (HIV)-positivity
  • Sentinel lymph node biopsy
  • Renal insufficiency (glomerular filtration rate (GFR) < 30 mL/min/1.73 m^2) measured within the past 60 days which precludes safe administration of the contrast agent
  • On dialysis
  • Prior allergic reaction to gadolinium-based magnetic resonance (MR) contrast agents

Missouri

Saint Louis
Siteman Cancer Center at Christian Hospital
Status: ACTIVE
Contact: Foluso Olabisi Ademuyiwa
Phone: 314-362-7201
Siteman Cancer Center at Washington University
Status: ACTIVE
Contact: Foluso Olabisi Ademuyiwa
Phone: 314-362-7201

PRIMARY OBJECTIVE:

I. To determine whether neoadjuvant docetaxel and carboplatin will increase the pathologic complete response (pCR) rate in triple-negative breast cancer (TNBC) compared to historical controls.

EXPLORATORY OBJECTIVES:

I. To determine the xenografting rate from TNBC patients being treated with neoadjuvant chemotherapy.

II. To compare chemotherapy responses in patient-derived xenografts (PDX) and TNBC patients being treated with neoadjuvant chemotherapy.

III. To investigate genomic and proteomic molecular changes in PDX and corresponding host patients with the intent to identify predictors of drug response and resistance.

IV. To assess the utility of multi-parametric fludeoxyglucose F-18-positron emission tomography (FDG-PET)/magnetic resonance (MR) imaging in predicting response to therapy after one cycle of therapy.

V. Measure circulating tumor deoxyribonucleic acid (DNA) (ctDNA) somatic mutations in serial plasma samples, and determine if ctDNA can predict clinical outcomes.

OUTLINE:

Patients receive docetaxel intravenously (IV) over 60 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery 3-5 weeks after the conclusion of chemotherapy.

After completion of study treatment, patients are followed up yearly for 5 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Foluso Olabisi Ademuyiwa

  • Primary ID 201404107
  • Secondary IDs NCI-2014-01037
  • Clinicaltrials.gov ID NCT02124902