Comparative Study on Two Post-operative Adjuvant Chemotherapy Regimens for Treating Triple-negative Breast Cancer

Sponsor

China Breast Cancer Clinical Study Group (Other)

Overall Status

Unknown status

CT.gov ID

NCT01642771

Collaborator

(none)

636

Enrollment

Locations

Arms

Duration (Months)

17.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: 5-Fu/epirubicin/CTX following Docetaxel Drug: Docetaxel/capecitabine followed by XEC	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

636 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

May 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 5-Fu/epirubicin/CTX following Docetaxel Docetaxel for the first 3 cycles of chemotherapy followed by 3 cycles of FEC (Fluorouracil, epirubicin and cyclophosphamide) chemotherapy	Drug: 5-Fu/epirubicin/CTX following Docetaxel Cycle 1-3: Docetaxel i.v. 75mg/m2 (One cycle = 21 days); Cycle 4-6: Fluorouracil i.v. 500 mg/m2, Epirubicin i.v. 75 mg/m2, Cyclophosphamide i.v. 500 mg/m2 (One cycle = 21 days) Other Names: Fluorouracil: 5-Fu
Experimental: Docetaxel/capecitabine followed by XEC Docetaxel/ capecitabine (TX) for the first 3 cycles of chemotherapy followed by 3 cycles of capecitabine/epirubicin/cyclophosphamide (XEC) chemotherapy	Drug: Docetaxel/capecitabine followed by XEC Cycle 1-3: Docetaxel i.v. 75 mg/m2, Capecitabine, p.o., 1000 mg/m2，b.i.d (take Capecitabine for 2 weeks and withdraw for 1 week) (One cycle = 21 days); Cycle 4-6: Capecitabine, i.v. 1000 mg/m2, b.i.d (take for 2 weeks and withdraw for 1 week),Epirubicin, i.v. 75 mg/m2, Cyclophosphamide, i.v. 500 mg/m2 (One cycle = 21 days) Other Names: Capecitabine: Xeloda

Arm

Intervention/Treatment

Active Comparator: 5-Fu/epirubicin/CTX following Docetaxel

Docetaxel for the first 3 cycles of chemotherapy followed by 3 cycles of FEC (Fluorouracil, epirubicin and cyclophosphamide) chemotherapy

Drug: 5-Fu/epirubicin/CTX following Docetaxel

Cycle 1-3: Docetaxel i.v. 75mg/m2 (One cycle = 21 days); Cycle 4-6: Fluorouracil i.v. 500 mg/m2, Epirubicin i.v. 75 mg/m2, Cyclophosphamide i.v. 500 mg/m2 (One cycle = 21 days)

Other Names:

Fluorouracil: 5-Fu

Experimental: Docetaxel/capecitabine followed by XEC

Docetaxel/ capecitabine (TX) for the first 3 cycles of chemotherapy followed by 3 cycles of capecitabine/epirubicin/cyclophosphamide (XEC) chemotherapy

Drug: Docetaxel/capecitabine followed by XEC

Cycle 1-3: Docetaxel i.v. 75 mg/m2, Capecitabine, p.o., 1000 mg/m2，b.i.d (take Capecitabine for 2 weeks and withdraw for 1 week) (One cycle = 21 days); Cycle 4-6: Capecitabine, i.v. 1000 mg/m2, b.i.d (take for 2 weeks and withdraw for 1 week),Epirubicin, i.v. 75 mg/m2, Cyclophosphamide, i.v. 500 mg/m2 (One cycle = 21 days)

Other Names:

Capecitabine: Xeloda

Outcome Measures

Primary Outcome Measures

5-year disease free survival [5 year after the completion of chemotherapy]
Including local relapse, distant metastasis, contralateral breast cancer, second primary cancer or death from any cause

Secondary Outcome Measures

Number of Participants with Adverse Events as a Measure of Safety [Within 5 years after the completion of chemotherapy]
Safety will be evaluated based on adverse events observed and the number of participants with adverse events. Blood biological tests shall also be conducted for further examination.
FACT-B scale scores as a Measure of living quality [Baseline, Week 0]
FACT-B scale scores of participants would be assessed to reflect their living quality.
5-year relapse free survival, distant disease free survival and overall survival as measures of efficacy [Within 5 years after the completion of chemotherapy]
Disease relapse shall be considered as the endpoint of relapse free survival and the period between surgery and disease relapse shall be recorded as a measure of efficacy. Also disease distant metastasis shall be considered as the endpoint of distant disease free survival and the period between surgery and Disease distant metastasis shall be recorded as a measure of efficacy.
FACT-B scale scores as a Measure of living quality [Week 9]
FACT-B scale scores of participants would be assessed to reflect their living quality.
FACT-B scale scores as a Measure of living quality [Week 18]
FACT-B scale scores of participants would be assessed to reflect their living quality.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing	China	100021
2	Pekingn Union Medical College Hospital	Beijing	Beijing	China	100032
3	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing	China	100050
4	PLA 307 Hospital	Beijing	Beijing	China	100071
5	The General Hospital of the People's Liberation Army	Beijing	Beijing	China	100853
6	The First Affi liated Hospital of Chongqing Medical University	Chongqing	Chongqing	China	400016
7	South West Hospital	Chongqing	Chongqing	China	400038
8	Gansu Cancer Hospital	Lanzhou	Gansu	China	730050
9	Guangdong Provincial Hospital of Traditional Chinese Medicine	Guangzhou	Guangdong	China	510120
10	Second Affiliated Hospital of Zhongshan University	Guangzhou	Guangdong	China	510120
11	Cancer Hospital of Shantou Medical College	Shantou	Guangdong	China	515041
12	Affiliated Hospital of Guiyang Medical College	Guiyang	Guizhou	China	550002
13	The Fourth Clinical Medical College of Hebei Medical University	Shijiazhuang	Hebei	China	050011
14	The second affiliated hospital of Harbin Medical University	Harbin	Heilongjiang	China	150001
15	The third affiliated hospital of Harbin Medical University	Harbin	Heilongjiang	China	150040
16	Henan cancer hospital affiliated to Zhengzhou university	Zhengzhou	Henan	China	450008
17	Hubei General Hospital	Wuhan	Hubei	China	430070
18	Xiangya Hospital Central-south University	Changsha	Hunan	China	410008
19	Jiangsu Cancer Hospital	Suzhou	Jiangsu	China	210000
20	Jiangsu Province Hospital	Suzhou	Jiangsu	China	210029
21	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China	215004
22	Third Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330009
23	Jinlin Cancer Hospital & Institute	Changchun	Jilin	China	130012
24	The First Hospital of Jilin University	Changchun	Jilin	China	130021
25	The First Hospital of China Medical University	Shenyang	Liaoning	China	110001
26	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China	200032
27	Zhongshan Hospital, Fudan University	Shanghai	Shanghai	China	200032
28	Huashan Hospital, Fudan University	Shanghai	Shanghai	China	200040
29	Shanghai 6th People's Hospital	Shanghai	Shanghai	China	200233
30	Changhai Hospital of Shanghai	Shanghai	Shanghai	China	200433
31	Shanxi Cancer Hospital	Taiyuan	Shanxi	China	030013
32	Second Affiliated Hospital of Medical College of Xi'An Jiaotong University	Xi'an	Shanxi	China	710004
33	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin	China	300060
34	Xinjiang Cancer Hospital	Wulumuqi	Xinjiang	China	830000
35	Zhejiang First Hospital	Hangzhou	Zhejiang	China	310003
36	Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310009
37	The First Hospital of Wenzhou Medical College	Wenzhou	Zhejiang	China	325000