Clinical trial NCT01642771: Comparative Study on Two Post-operative Adjuvant Chemotherapy Regimens for Treating Triple-negative Breast Cancer
Official title: A Prospective, Randomized, Open, Multi-center Phase III Clinical Study Comparing Efficacy and Safety of Sequential T-FEC and TX-XEC as Post-operative Adjuvant Chemotherapy Options for the Treatment of Triple-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Triple-negative Breast Cancer
Post-operative adjuvant Chemotherapy
Docetaxel
Capecitabine
Epirubicin
Cyclophosphamide
Fluorouracil
Lead sponsor: China Breast Cancer Clinical Study Group
Sponsor class: OTHER
First posted: 2012-07-17
Enrollment: 636
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: Recent clinical studies showed that triple-negative breast cancer patients (ER-/PR-/HER2-) may benefit more from Capecitabine chemotherapy. However, the optimum post-operative adjuvant Capecitabine chemotherapy regimen has not been determined for Chinese population with triple-negative breast cancer. Thus it's necessary to conduct a multi-center Phase III clinical trial to verify efficacy and safety of Capecitabine in the treatment of triple-negative breast cancer. In this study, a prospective, randomized, open, multi-center Phase III clinical study was conducted to compare efficacy and safety of sequential Docetaxel followed by Fluorouracil/Epirubicin/Cyclophosphamide (FEC) and sequential Docetaxel and Capecitabine followed by Capecitabine/Epirubicin/Cyclophosphamide (XEC) as post-operative adjuvant chemotherapy in the treatment of triple-negative breast cancer in Chinese population.

Detailed description: Post-operative adjuvant chemotherapy has been shown to improve overall survival, delay local relapse and reduce distant metastasis by multiple large-scale prospective clinical trial. In registry clinical trial for Capecitabine conducted by O Shaughnessy, it revealed that a combined chemotherapy of Capecitabine and Docetaxel achieved better outcomes compared with Docetaxel alone. And the significant effect of Capecitabine was also evidenced by CHAT trial in which Trastuzumab/Docetaxel/Capecitabine regimen was proved to perform greater than Trastuzumab/Docetaxel regimen. In addition to better outcomes, Capecitabine also showed good tolerance and safety profile. In 2009, Finnish Breast Cancer Group published their study results from FinXX clinical trial on Lancet Oncology, and in this trial, they compared the efficacy between sequential Docetaxel (3 cycles) followed by 3 cycles of Fluorouracil/Epirubicin/Cyclophosphamide (FEC) and sequential Docetaxel and Capecitabine (3 cycles) followed by 3 cycles of Capecitabine/Epirubicin/Cyclophosphamide (XEC) in lymph positive or high-risk lymph negative early-stage breast cancer patients. And their results showed a better outcome in TX-XEC regimen. 5-year follow-up analysis of this trial revealed that combined Capecitabine regimen can bring more significant clinical benefits to triple-negative breast cancer patients. Another clinical trial NO1062 released their preliminary results on comparison of AC-T and AC-XT regimens and it showed that combined Capecitabine regimen can significantly improve overall survival and this effect is more obvious in triple--negative breast cancer patients.

Based on the results of FinXX and NO1062, it's of great value to optimize combined Capecitabine regimen and clarify involved questions, such as whether the efficacy of Capecitabine is related to its treatment course or not, whether Capecitabine should be combined into current standardized chemotherapy or a sequential therapy. Also, there are still no clear conclusions on the best post-operative adjuvant chemotherapy for triple--negative breast cancer patients. Especially in Chinese population, the efficacy and safety of Capecitabine in adjuvant chemotherapy has not been well established. So it's necessary to explore reasonable dosage, safety profile and efficacy of combined Capecitabine therapy. Based on this purpose, this study is hoped to compare efficacy and safety of sequential Docetaxel followed by Fluorouracil/Epirubicin/Cyclophosphamide (FEC) and sequential Docetaxel and Capecitabine followed by Capecitabine/Epirubicin/Cyclophosphamide (XEC) as post-operative adjuvant chemotherapy in the treatment of triple-negative breast cancer in Chinese population.

Eligibility criteria: Inclusion Criteria:

* Female aged 18 - 70 years old;
* Histological confirmed with unilateral invasive carcinoma (all pathological types are applicable);
* Newly diagnosed conditions allowing direct surgery without any absolute contraindication for surgery;
* No mass or microscopic tumor residue after surgery resection;
* Initiate adjuvant chemotherapy within 30 days after surgery;
* Axillary lymph node positive (including the sentinel lymph node positive and lymph node positive after axillary dissection), for example, axillary lymph node negative requires that primary tumor size must be greater than 1cm;
* Definite reports on ER/PR/Her2 receptor showing all ER/PR/Her2 negative (specific definitions: immunohistochemical detection of ER \<10% tumor cells is defined as ER negative, PR \<10% positive tumor cells is defined as PR-negative, Her2 is 0\~1+ or 2+ but determined negative via FISH or CISH detected (no amplification) is defined as Her2 negative);
* No relevant clinical or imaging evidence of metastasis showing in the preoperative examination (M0);
* Without peripheral neuropathy;
* ECOG performance score is 0 or 1;
* Postoperative recovery was good and an interval of at least one week since the surgery is necessary;
* White blood cell count\> 4 × 10\^9/l, neutrophil count\> 2 × 10\^9/l, platelet count\> 100 × 10\^9/l and hemoglobin 9g/dl);
* ASAT and ALAT \<1.5 folds of the upper limit of normal values, alkaline phosphatase \<2.5 folds of the upper limit of normal values, total bilirubin \<1.5 folds of the upper limit of normal values;
* Serum creatinine \<1.5 folds of the upper limit of normal value;
* Women at childbearing age should take contraception measures during treatment;
* Cardiac function: echocardiographic examination showed LEVF\> 50%;
* Informed consent form signed. -

Exclusion Criteria:

* Bilateral breast cancer or carcinoma in situ (DCIS / LCIS);
* Metastasis at any location;
* Any tumor \> T4a (UICC1987) (accompanied by skin involvement, lump adhesion and fixation, inflammatory breast cancer);
* Any of ER, PR or Her-2 is positive;
* Contralateral breast clinically or radiologically suspected to be malignant but not confirmed which needs a biopsy;
* Previous neoadjuvant therapy, including chemotherapy, radiotherapy and hormone therapy;
* Previously suffering from malignant tumors (except for basal cell carcinoma and cervical carcinoma in situ), including contralateral breast cancer;
* Already enrolled into other clinical trials;
* Severe systemic disease and/or uncontrollable infection, unable to be enrolled in this study
* LEVF \<50% (echocardiography);
* Suffering from severe cardiovascular and cerebrovascular diseases within six months before the randomization (such as: unstable angina, chronic heart failure, uncontrollable high blood pressure \> 150/90mmHg, myocardial infarction or brain vascular accident);
* Known allergic to taxane and anthracycline agents;
* Women at childbearing age refuse to take contraception measures during the treatment and 8 weeks after completion of treatment;
* Pregnant and breast-feeding women;
* Pregnancy test showed positive results before drug administration after enrolling in to the study;
* With mental illness and cognitive impairment, unable to understand trial protocol and side effects and complete trial protocol and follow-ups (systematic evaluation is required before recruiting into this study);
* Without personal freedom and independent civil capacity.

Primary outcomes:
measure: 5-year disease free survival
timeFrame: 5 year after the completion of chemotherapy
Secondary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety
timeFrame: Within 5 years after the completion of chemotherapy
measure: FACT-B scale scores as a Measure of living quality
timeFrame: Baseline, Week 0
measure: 5-year relapse free survival, distant disease free survival and overall survival as measures of efficacy
timeFrame: Within 5 years after the completion of chemotherapy
measure: FACT-B scale scores as a Measure of living quality
timeFrame: Week 9
measure: FACT-B scale scores as a Measure of living quality
timeFrame: Week 18
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Pekingn Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: PLA 307 Hospital
state: Beijing
city: Beijing
country: China
facility: The General Hospital of the People's Liberation Army
state: Beijing
city: Chongqing
country: China
facility: The First Affi liated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: South West Hospital
state: Chongqing
city: Lanzhou
country: China
facility: Gansu Cancer Hospital
state: Gansu
city: Guangzhou
country: China
facility: Guangdong Provincial Hospital of Traditional Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Second Affiliated Hospital of Zhongshan University
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou Medical College
state: Guangdong
city: Guiyang
country: China
facility: Affiliated Hospital of Guiyang Medical College
state: Guizhou
city: Shijiazhuang
country: China
facility: The Fourth Clinical Medical College of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: The second affiliated hospital of Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: The third affiliated hospital of Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan cancer hospital affiliated to Zhengzhou university
state: Henan
city: Wuhan
country: China
facility: Hubei General Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central-south University
state: Hunan
city: Suzhou
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: Third Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jinlin Cancer Hospital & Institute
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai 6th People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Changhai Hospital of Shanghai
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Xi'an
country: China
facility: Second Affiliated Hospital of Medical College of Xi'An Jiaotong University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Wulumuqi
country: China
facility: Xinjiang Cancer Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang First Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The First Hospital of Wenzhou Medical College
state: Zhejiang
Study officials:
affiliation: China Breast Cancer Clinical Study Group
name: Zhimin Shao, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bria E, Nistico C, Cuppone F, Carlini P, Ciccarese M, Milella M, Natoli G, Terzoli E, Cognetti F, Giannarelli D. Benefit of taxanes as adjuvant chemotherapy for early breast cancer: pooled analysis of 15,500 patients. Cancer. 2006 Jun 1;106(11):2337-44. doi: 10.1002/cncr.21886.
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citation: Wardley AM, Pivot X, Morales-Vasquez F, Zetina LM, de Fatima Dias Gaui M, Reyes DO, Jassem J, Barton C, Button P, Hersberger V, Torres AA. Randomized phase II trial of first-line trastuzumab plus docetaxel and capecitabine compared with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer. J Clin Oncol. 2010 Feb 20;28(6):976-83. doi: 10.1200/JCO.2008.21.6531. Epub 2009 Dec 28.
citation: Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtio K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, Leinonen M, Lindman H; FinXX Study Investigators. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol. 2009 Dec;10(12):1145-51. doi: 10.1016/S1470-2045(09)70307-9. Epub 2009 Nov 10.
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