Discovery and Validate of Multi-genetic Biomarkers for Capecitabine in Chinese Colorectal Patients

Colorectal Cancer Clinical Trial

Official title:

Discovery and Validate of Multi-genetic Biomarkers for Capecitabine in Chinese Colorectal Patients

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03030508
• Other study ID #: WChen
• Status: Enrolling by invitation
• Phase: N/A
• First received: January 13, 2017
• Last updated: January 22, 2017
• Start date: January 2016
• Est. completion date: March 2019

Study information

• Verified date: January 2017
• Source: Shanghai Changzheng Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

At present, chemotherapy is widely used in the adjuvant treatment of colorectal cancer patients after surgery. Capecitabine is one of the main chemotherapeutic drugs. But the effect is not good enough, the adverse reaction is serious, and the individual differences were significant. The present study shows that these problems are related to the differences in the exposure of capecitabine and its metabolites in different patients. The genetic biomarkers for capecitabine include DRD, MTHFR and TYMS. Mutations in these genes directly affect the expression of metabolic enzymes involved in capecitabine and control the concentration of capecitabine and its metabolites. However, these markers have been obtained through clinical trials in the United States, and their role in predicting the effectiveness or safety of capecitabine and its metabolites has not been validated in Chinese cancer patients.The study was based on a case study of patients with colorectal cancer in China, and capecitabine as the primary postoperative chemotherapy regimen to verify whether the available biomarkers can be used to predict the effectiveness and safety of capecitabine. To clarify the effect of capecitabine on endogenous metabolites, and to study the mechanism of its effect, so as to discover new biomarkers.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 300
• Est. completion date: March 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. more than 18 years old;

2. patients with colon cancer diagnosed by biopsy (regardless of cancer stage);

3. received postoperative containing capecitabine chemotherapy;

4. volunteer to participate in the experiment

Exclusion Criteria:

1. pregnant and lactating women;

2. patients with hypersensitivity to fluorouracil or severe metabolic failure;

3. patients with severe infection;

4. patients with other cancers other than colorectal cancer within the first five years of colorectal cancer surgery;

Related Conditions & MeSH terms

• Capecitabine
• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Other:
• No intervention

Locations

Country	Name	City	State
China	Department of medicine of Shanghai Changzheng Hospital	Shanghai	Shanghai

Sponsors (6)

Lead Sponsor	Collaborator
Shanghai Changzheng Hospital	Changhai Hospital, Shanghai Minhang Central Hospital, The 97 Hospital of chinese PLA, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Xuzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (7)

Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, Smits PH, Rosing H, Mandigers CM, Soesan M, Beijnen JH, Schellens JH. Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis. J Clin Oncol. 2016 Jan 20;34(3):227-34. doi: 10.1200/JCO.2015.63.1325. — View Citation

Denkert C, Bucher E, Hilvo M, Salek R, Orešic M, Griffin J, Brockmöller S, Klauschen F, Loibl S, Barupal DK, Budczies J, Iljin K, Nekljudova V, Fiehn O. Metabolomics of human breast cancer: new approaches for tumor typing and biomarker discovery. Genome Med. 2012 Apr 30;4(4):37. — View Citation

Huang L, Chen F, Chen Y, Yang X, Xu S, Ge S, Fu S, Chao T, Yu Q, Liao X, Hu G, Zhang P, Yuan X. Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines. Sci Rep. 2014 Jul 16;4:5697. doi: 10.1038/srep05697. — View Citation

Ikeda K, Oike Y, Shimizu T, Taguchi R. Global analysis of triacylglycerols including oxidized molecular species by reverse-phase high resolution LC/ESI-QTOF MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Sep 1;877(25):2639-47. doi: 10.1016/j.jchromb.2009.03.047. — View Citation

Li F, Qin X, Chen H, Qiu L, Guo Y, Liu H, Chen G, Song G, Wang X, Li F, Guo S, Wang B, Li Z. Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom. 2013 Jan 15;27(1):24-34. doi: 10.1002/rcm.6420. — View Citation

Wu CW, Ng SS, Dong YJ, Ng SC, Leung WW, Lee CW, Wong YN, Chan FK, Yu J, Sung JJ. Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut. 2012 May;61(5):739-45. doi: 10.1136/gut.2011.239236. — View Citation

Zhang X, Sun B, Lu Z. Evaluation of clinical value of single nucleotide polymorphisms of dihydropyrimidine dehydrogenase gene to predict 5-fluorouracil toxicity in 60 colorectal cancer patients in China. Int J Med Sci. 2013 May 20;10(7):894-902. doi: 10.7150/ijms.5556. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Adverse Events That Are Related to Treatment	during chemotherapy
Primary	Disease-free survival		Three year disease-free survival
Secondary	Three year disease free survival rate		Three year disease free survival rate