microRNA of Human Epidermal Growth Factor Receptor 2 （HER2）Positive Patient Treated With Herceptin

Breast Cancer Clinical Trial

Official title:

A Perspective Study of the Predictive Value of microRNA in Patients With HER2 Positive Advanced Stage Breast Cancer Who Were Treated With Herceptin

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02656589
• Other study ID #: SSC201512
• Status: Recruiting
• Phase: N/A
• First received: January 8, 2016
• Last updated: October 12, 2016
• Start date: June 2015
• Est. completion date: June 2018

Study information

• Verified date: October 2016
• Source: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Contact: Erwei Song, Ph.D
• Phone: 86-20-81332576
• Email: songerwei02[@]yahoo.com.cn
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Guangdong Province
• Study type: Observational

Clinical Trial Summary

This projective observational study is planned to enroll more than 300 advanced breast cancer patients, who were proved as Her-2 positive using fluorescence in situ hybridization (FISH) and / or immunohistochemistry, and 100 healthy donors as control. Before treatment, the plasma microRNA will be collected and detected by microRNA extraction kit and quantitative polymerase chain reaction (qPCR), respectively. After analyzed their microRNA expression by microRNA predictive model, previously reported by our team, all of enrolled patients will be classified as "probable sensitive group" or "probable resistant group". Herceptin combined with other chemotherapy will be the backbone of salvage treatment and used for at least 3 months; the change of local masses and metastasis lesions after treatment will be documented to evaluate the response. Based on these results, investigator aim to construct a mathematical predictive model by analyzing the correlation of baseline microRNA expression level and the prognosis of patients. And a diagnosis microRNA kit will be planned and manufactured

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. The patients signed the written informed consent

2. female patient who is = 18yrs,

3. HER2 positive: immunohistochemistry (+++) or FISH (+)

4. stage IV

5. the patients have no history of chemotherapy ,hormone therapy,radiotherapy or surgery after diagnosis of breast cancer

6. the result of patients' blood tests are as follow: WBC=3.0×109/L; Plt=100×109/L;AST/SGOT or ALT/AGPT=tripple of normal upper limit; Creatinine<double of the normal upper limit

7. ECOG scores are 0 or 1 .

8. The patient is able to take oral pills

Exclusion Criteria:

1. The patient was never exposed to herceptin.

2. The patient suffered from other non-breast malignancy in the last 5 years, except for cervical carcinoma in situ, radical basal cell carcinoma or squamous cell carcinoma.

3. The life expectancy is less than 3 months.

4. Severe hepatic function disorder, Child Pugh grade C.

5. Severe cardiac function disorder, cardiac function is more than grade III;

6. Prolonged QT interval;

7. Arrhythmia or taking anti-arrhythmia drugs;

8. Pregnant or breast feeding female.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Capecitabine
Capecitabine will be administered orally at a dose of 2500mg/m2 daily for 3 months (Day 1 to 14 of a 21-day cycle)
• Trastuzumab
patients will receive herceptin intravenous infusion at a dose of 6mg on day 1 of each cycle

Locations

Country	Name	City	State
China	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	Guangzhou	Guangdong

Sponsors (6)

Lead Sponsor	Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	Huiping Li,M.D., Ph.D.,Peking University Cancer Hospital, Huiyun Wang,Ph.D., Sun Yat-Sen University, Jiang Liu,M.B., Sun Yat-Sen University, Jianing Chen,M.B., Sun Yat-Sen University, Shicheng Su, M.D., Ph.D., Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (17)

Chan M, Liaw CS, Ji SM, Tan HH, Wong CY, Thike AA, Tan PH, Ho GH, Lee AS. Identification of circulating microRNA signatures for breast cancer detection. Clin Cancer Res. 2013 Aug 15;19(16):4477-87. doi: 10.1158/1078-0432.CCR-12-3401. Epub 2013 Jun 24. — View Citation

Gururajan M, Josson S, Chu GC, Lu CL, Lu YT, Haga CL, Zhau HE, Liu C, Lichterman J, Duan P, Posadas EM, Chung LW. miR-154* and miR-379 in the DLK1-DIO3 microRNA mega-cluster regulate epithelial to mesenchymal transition and bone metastasis of prostate can — View Citation

Hur K, Toiyama Y, Schetter AJ, Okugawa Y, Harris CC, Boland CR, Goel A. Identification of a metastasis-specific MicroRNA signature in human colorectal cancer. J Natl Cancer Inst. 2015 Feb 6;107(3). pii: dju492. doi: 10.1093/jnci/dju492. Print 2015 Mar. — View Citation

Jackson DB. Serum-based microRNAs: are we blinded by potential? Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):E5. doi: 10.1073/pnas.0809999106. Epub 2008 Dec 23. — View Citation

Jiang L, Cheng Q, Zhang BH, Zhang MZ. Circulating microRNAs as biomarkers in hepatocellular carcinoma screening: a validation set from China. Medicine (Baltimore). 2015 Mar;94(10):e603. doi: 10.1097/MD.0000000000000603. — View Citation

Kleivi Sahlberg K, Bottai G, Naume B, Burwinkel B, Calin GA, Børresen-Dale AL, Santarpia L. A serum microRNA signature predicts tumor relapse and survival in triple-negative breast cancer patients. Clin Cancer Res. 2015 Mar 1;21(5):1207-14. doi: 10.1158/1 — View Citation

Li A, Yu J, Kim H, Wolfgang CL, Canto MI, Hruban RH, Goggins M. Serum miR-1290 as a marker of pancreatic cancer--response. Clin Cancer Res. 2013 Sep 15;19(18):5252-3. doi: 10.1158/1078-0432.CCR-13-1899. Epub 2013 Jul 23. — View Citation

Li J, Wang Y, Yu W, Chen J, Luo J. Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance. Biochem Biophys Res Commun. 2011 Mar 4;406(1):70-3. doi: 10.1016/j.bbrc.2011.01.111. Epub 2011 Feb 3. — View Citation

Li LM, Hu ZB, Zhou ZX, Chen X, Liu FY, Zhang JF, Shen HB, Zhang CY, Zen K. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res. 2010 Dec 1;70(23):9798-807. doi: 10.1158/0008-5472.CA — View Citation

Masuda S, Izpisua Belmonte JC. Re: Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst. 2014 Mar;106(3):djt457. doi: 10.1093/jnci/djt457. Epub 2014 Mar 1. — View Citation

Parpart S, Roessler S, Dong F, Rao V, Takai A, Ji J, Qin LX, Ye QH, Jia HL, Tang ZY, Wang XW. Modulation of miR-29 expression by a-fetoprotein is linked to the hepatocellular carcinoma epigenome. Hepatology. 2014 Sep;60(3):872-83. doi: 10.1002/hep.27200. — View Citation

Roth C, Rack B, Müller V, Janni W, Pantel K, Schwarzenbach H. Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res. 2010;12(6):R90. doi: 10.1186/bcr2766. Epub 2010 Nov 3. — View Citation

Schwarzenbach H, Nishida N, Calin GA, Pantel K. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014 Mar;11(3):145-56. doi: 10.1038/nrclinonc.2014.5. Epub 2014 Feb 4. Review. — View Citation

van Schooneveld E, Wouters MC, Van der Auwera I, Peeters DJ, Wildiers H, Van Dam PA, Vergote I, Vermeulen PB, Dirix LY, Van Laere SJ. Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in ser — View Citation

Wang Y, Gu J, Roth JA, Hildebrandt MA, Lippman SM, Ye Y, Minna JD, Wu X. Pathway-based serum microRNA profiling and survival in patients with advanced stage non-small cell lung cancer. Cancer Res. 2013 Aug 1;73(15):4801-9. doi: 10.1158/0008-5472.CAN-12-32 — View Citation

Xiang M, Zeng Y, Yang R, Xu H, Chen Z, Zhong J, Xie H, Xu Y, Zeng X. U6 is not a suitable endogenous control for the quantification of circulating microRNAs. Biochem Biophys Res Commun. 2014 Nov 7;454(1):210-4. doi: 10.1016/j.bbrc.2014.10.064. Epub 2014 O — View Citation

Zhai R, Wei Y, Su L, Liu G, Kulke MH, Wain JC, Christiani DC. Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma: the influence of Helicobacter pylori infection status. Carcinogenesis. 2015 Jan;36(1):87-93. doi: 10.109 — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progress-free survival of patients		progression free survival (PFS) was defined as the interval from the diagnosis of advanced breast cancer with HER2 positive to disease progression, relapse, death due to any causes or last follow-up.The follow-up interval is 2 years.	No
Primary	overall survival of patients		Overall survival was defined as the interval from the diagnosis of advanced breast cancer with HER2 positive to death due to any causes or last follow-up,The follow-up interval is 2 years.	No