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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01642771
• Other study ID #: EBC protocol 1.1
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 4, 2012
• Last updated: April 18, 2017
• Start date: June 2012
• Est. completion date: May 2020

Study information

• Verified date: April 2017
• Source: China Breast Cancer Clinical Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 636
• Est. completion date: May 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

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)
• 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)

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Pekingn Union Medical College Hospital	Beijing	Beijing
China	PLA 307 Hospital	Beijing	Beijing
China	The General Hospital of the People's Liberation Army	Beijing	Beijing
China	Jinlin Cancer Hospital & Institute	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	Xiangya Hospital Central-south University	Changsha	Hunan
China	South West Hospital	Chongqing	Chongqing
China	The First Affi liated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Guangdong Provincial Hospital of Traditional Chinese Medicine	Guangzhou	Guangdong
China	Second Affiliated Hospital of Zhongshan University	Guangzhou	Guangdong
China	Affiliated Hospital of Guiyang Medical College	Guiyang	Guizhou
China	Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang First Hospital	Hangzhou	Zhejiang
China	The second affiliated hospital of Harbin Medical University	Harbin	Heilongjiang
China	The third affiliated hospital of Harbin Medical University	Harbin	Heilongjiang
China	Gansu Cancer Hospital	Lanzhou	Gansu
China	Third Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Changhai Hospital of Shanghai	Shanghai	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Huashan Hospital, Fudan University	Shanghai	Shanghai
China	Shanghai 6th People's Hospital	Shanghai	Shanghai
China	Zhongshan Hospital, Fudan University	Shanghai	Shanghai
China	Cancer Hospital of Shantou Medical College	Shantou	Guangdong
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	The Fourth Clinical Medical College of Hebei Medical University	Shijiazhuang	Hebei
China	Jiangsu Cancer Hospital	Suzhou	Jiangsu
China	Jiangsu Province Hospital	Suzhou	Jiangsu
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Shanxi Cancer Hospital	Taiyuan	Shanxi
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	The First Hospital of Wenzhou Medical College	Wenzhou	Zhejiang
China	Hubei General Hospital	Wuhan	Hubei
China	Xinjiang Cancer Hospital	Wulumuqi	Xinjiang
China	Second Affiliated Hospital of Medical College of Xi'An Jiaotong University	Xi'an	Shanxi
China	Henan cancer hospital affiliated to Zhengzhou university	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
China Breast Cancer Clinical Study Group

Country where clinical trial is conducted

China, 

References & Publications (7)

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. — View 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, Lehtiö 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. — View Citation

Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. — View Citation

O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002 Jun 15;20(12):2812-23. — View Citation

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Rüschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD; Herceptin Adjuvant (HERA) Trial Study Team.. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72. — View Citation

Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 Dec 20;24(36):5664-71. Epub 2006 Nov 20. — View Citation

Wardley AM, Pivot X, Morales-Vasquez F, Zetina LM, de Fátima 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-year disease free survival	Including local relapse, distant metastasis, contralateral breast cancer, second primary cancer or death from any cause	5 year after the completion of chemotherapy
Secondary	Number of Participants with Adverse Events as a Measure of Safety	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.	Within 5 years after the completion of chemotherapy
Secondary	FACT-B scale scores as a Measure of living quality	FACT-B scale scores of participants would be assessed to reflect their living quality.	Baseline, Week 0
Secondary	5-year relapse free survival, distant disease free survival and overall survival as measures of efficacy	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.	Within 5 years after the completion of chemotherapy
Secondary	FACT-B scale scores as a Measure of living quality	FACT-B scale scores of participants would be assessed to reflect their living quality.	Week 9
Secondary	FACT-B scale scores as a Measure of living quality	FACT-B scale scores of participants would be assessed to reflect their living quality.	Week 18