Clinical trial NCT02455141: Adjuvant Treatment of EC Followed by Taxane +/- Carboplatin in Triple-Negative Breast Cancer
Official title: Epirubicin-Cyclophosphamide Followed by Taxanes or Taxanes Plus Carboplatin in Triple-Negative Breast Cancer：A Prospective, Randomized, Phase III Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Neoplasm
Keywords: chemptherapy
triple negative
taxanes
carboplatin
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2015-05-27
Enrollment: 970
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare disease-free survival (DFS) rate of adjuvant chemotherapy epirubicin-cyclophosphamide followed by weekly paclitaxel or docetaxel (EC-T), or weekly paclitaxel or docetaxel-carboplatin (EC-TCb) in triple-negative breast cancer.

Detailed description: This study plans to enroll triple-negative breast cancer patients who have complete tumor removal. Patients are randomized to receive either EC-wP/T or EC-wP/TCb adjuvant chemotherapy. For triple-negative breast cancer, a subgroup of triple-negative breast cancer has DNA repairement deficiency and adding carboplatin to paclitaxel may improve DFS on the basis of weekly paclitaxel adjuvant chemotherapy.

Eligibility criteria: Inclusion Criteria

* Histologically confirmed adenocarcinoma of the breast, completely tumor removal by either modified radical mastectomy or local excision plus axillary lymph node dissection (i.e., breast conservation therapy) or sentinel node biopsy. (Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for lobular carcinoma in situ (less than 1 mm allowed);
* Tumor specimens are available for estrogen receptor (ER), progesterone receptor (PgR) and Her2 (human epidermal-growth-factor receptor 2) detection, patients should be with triple negative breast cancer. Triple-negative disease is defined as ER \<10% positivity, PgR \<10% positivity, and negativity for Her2 (IHC (immunohistochemistry) 0-1+ or FISH (fluorescence in situ hybridization) negative);
* Adequate bone marrow function
* Adequate liver and renal function
* Eastern Cooperative Oncology Group (ECOG) Performance Score 0-1;
* Women with potential child-bearing must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable method of birth control to avoid pregnancy for the duration of the study;
* Written informed consent according to the local ethics committee requirements.

Exclusion Criteria:

* Prior systemic of breast cancer, including chemotherapy;
* Metastatic breast cancer;
* With a history of malignant tumor except uterine cervix cancer in situ or skin basal cell carcinoma;
* Patients with medical conditions that indicate intolerant to adjuvant therapy and related treatment, including uncontrolled pulmonary disease, diabetes mellitus, severe infection, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease;
* Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive;
* Contraindication for using dexamethasone;
* History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction; poorly controlled hypertension (systolic BP\>180 mmHg or diastolic BP\>100 mmHg);
* Has peripheral neuropathy no less than grade 1;
* Patient is pregnant or breast feeding;
* Patients with psychiatric disorder or other diseases leading to incompliance to the therapy;
* Known severe hypersensitivity to any drugs in this study;
* Treatment with any investigational drugs within 30 days before the beginning of study treatment.

Primary outcomes:
measure: Disease-free survival
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 3 years
measure: Incidence of neutropenia fever
timeFrame: up to 7 months
measure: Incidence of grade 3-4 side effects
timeFrame: up to 7 months
Other outcomes:
Locations:
city: Fuding
country: China
facility: Fuding Hospital
state: Fujian
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Quanzhou
country: China
facility: Quanzhou First Hospital
state: Fujian
city: Foshan
country: China
facility: Foshan No.1 People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Maternal and Child Health Care Hospital
state: Guangdong
city: Harbin
country: China
facility: Cancer Hospital Affiliated to Harbin Medical University
state: Heilongjiang
city: Jiangyin
country: China
facility: Jiangsu Jiangyin People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First People's Hospital of Wujiang District
state: Jiangsu
city: Yancheng
country: China
facility: Yancheng Hospital of TCM
state: Jiangsu
city: Shanghai
country: China
facility: Obstetrics & Gynecology Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai JiaoTong University School of Medicine, Ruijin Hospital
state: Shanghai
city: Shanghai
country: China
facility: Central Hospital of Huangpu District, Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Shanghai International Peace Maternal and child health care hospital
state: Shanghai
city: Shanghai
country: China
facility: The Ninth People's Hospital of Shanghai
state: Shanghai
city: Hangzhou
country: China
facility: Hangzhou Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial Hospital of TCM
state: Zhejiang
city: Jiaxin
country: China
facility: Jiaxin Maternal and Child Health Care Hospital
state: Zhejiang
city: Lishui
country: China
facility: Lishui People's Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Medical Treatment Center Lihuili Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Women and Children's Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital
state: Zhejiang
city: Rui'an
country: China
facility: Rui'an People's Hospital
state: Zhejiang
city: Shaoxing
country: China
facility: Shaoxing Shangyu People's Hospital
state: Zhejiang
city: Shaoxing
country: China
facility: Shaoxing No.2 Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Central Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou People's Hospital
state: Zhejiang
city: Zhoushan
country: China
facility: Zhoushan Hospital
state: Zhejiang
Study officials:
affiliation: Affiliated Ruijin Hospital of Shanghai JiaoTong University School of Medicine
name: Kunwei Shen, professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, Broadwater G, Goldstein LJ, Martino S, Ingle JN, Henderson IC, Norton L, Winer EP, Hudis CA, Ellis MJ, Berry DA; Cancer and Leukemia Group B (CALGB) Investigators. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med. 2007 Oct 11;357(15):1496-506. doi: 10.1056/NEJMoa071167.
citation: Martin M, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodriguez CA, Crespo C, Abad M, Dominguez S, Florian J, Llorca C, Mendez M, Godes M, Cubedo R, Murias A, Batista N, Garcia MJ, Caballero R, de Alava E. Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat. 2010 Aug;123(1):149-57. doi: 10.1007/s10549-009-0663-z.
citation: Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. doi: 10.1200/JCO.2014.57.0572. Epub 2014 Aug 4.
citation: von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, Zahm DM, Kummel S, Eidtmann H, Klare P, Huober J, Costa S, Tesch H, Hanusch C, Hilfrich J, Khandan F, Fasching PA, Sinn BV, Engels K, Mehta K, Nekljudova V, Untch M. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014 Jun;15(7):747-56. doi: 10.1016/S1470-2045(14)70160-3. Epub 2014 Apr 30.
citation: Chen XS, Yuan Y, Garfield DH, Wu JY, Huang O, Shen KW. Both carboplatin and bevacizumab improve pathological complete remission rate in neoadjuvant treatment of triple negative breast cancer: a meta-analysis. PLoS One. 2014 Sep 23;9(9):e108405. doi: 10.1371/journal.pone.0108405. eCollection 2014.