Evaluation of Somatic Mutation Spectrum as Biomarker for Survival Outcome in Chinese CRC

Colorectal Cancer Clinical Trial

Official title:

A Cohort Study Evaluating the Effectiveness of the Somatic Mutation Spectrum Model in CRC Prognosis and Prediction Stratification

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04228614
• Other study ID #: mutation spectrum model-CRC
• Status: Recruiting
• Start date: May 1, 2018
• Est. completion date: May 1, 2021

Study information

• Verified date: January 2020
• Source: Sun Yat-sen University
• Contact: Feng Wang, MD.,PhD.
• Phone: +862087343795
• Email: wangfeng[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

By analyse the tissue/blood variant spectrum model using NGS, the present clinical trial aims to elucidate the genetic basis of CRC in Chinese; to establish of CRC genetic map in Chinese patients; to identification new genetic biomarkers, drug and pathways; and to subtyping for precision treatment and management for Chinese CRC patients.

Description:

Colorectal cancer (CRC), as one of the common malignant tumors with high morbidity and mortality, is a major health threat in China. Surgical resection is the conventional treatment for early and intermediate stage CRC, chemotherapy is the main treatment for late stage CRC.

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 170bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation. Although the mechanisms of its release have not been fully addressed, apoptosis and/or necrosis of tumor cells and serum exosome are considered as its main source, which makes it a genomic reservoir of different tumor clones. Also, as its half-life is up to hours, ctDNA is reflecting the most up-to-date status of tumor genome. Hence, it allows for noninvasive molecular characterization of tumors,which can be qualitative, quantitative and used for disease monitoring. The possibility of that ctDNA could be used to detect micrometastatic disease in patients received surgical resection was suggested in several studies. Using Next Generation Sequencing (NGS), Newman et al. have shown that the serum level of ctDNA was correlated with tumor progress and prognosis in NSCLC. Isaac et al. demonstrated the postoperative ctDNA level was associated with breast cancer progression, and it was more sensitive compared to CT scan for predicting the early relapse. Tie et al. examined the postoperative ctDNA level of 1046 plasma samples from a prospective cohort of 230 patients with resected stage II CRC by NGS, and their results demonstrated that recurrence happened in 79% of the patients with positive postoperative ctDNA at median follow-up of 27 months, versus 9.8% in the negative postoperative ctDNA group.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: May 1, 2021
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Retrospective cohort:

1. The patient had no previous history of tumor prior to the diagnosis of colorectal cancer.

2. The tissue samples of patients were obtained from the radical(stage I-III) or palliative (stage IV) resection of colorectal cancer.

3. The clinical data of patients are complete.

4. The treatment record of the patients after surgery are complete, and the fellow-up data are available.

Prospective cohort:

1. Patients who were diagnosed as stage IV colorectal cancer and planed to received palliative systematic chemotherapy.

2. Paired 10 ml blood and tissue samples should be available

3. The clinical informations of patients and definite pathological diagnosis of colorectal cancer should be obtained

4. Patients agree with the group to follow-up them and provide follow-up informations

5. Performance status ECOG(Eastern Cooperative Oncology Group) score =2

6. Informed consent must be obtained from the patient

Exclusion Criteria:

Retrospective cohort:

1. The patient had previous history of tumor prior to colorectal cancer surgery

2. The clinical data of patients are not available

4. The date of treatment after surgery are not integrity, outcome data are not available

Prospective cohort:

1. The patient received a blood transfusion within three months;

2. The patient has active HIV, hepatitis B or hepatitis C infection;

3. pregnant patients;

4. Alcohol or drug users;

5. Other situation that researchers considered might affect the results of the experiment or violate the ethics.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Locations

Country	Name	City	State
China	Medical Oncology,Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (6)

Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, Garrido JA, Dowsett M, Reis-Filho JS, Smith IE, Turner NC. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021. — View Citation

Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12. — View Citation

Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, Shrager JB, Loo BW Jr, Alizadeh AA, Diehn M. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014 May;20(5):548-54. doi: 10.1038/nm.3519. Epub 2014 Apr 6. — View Citation

Rolfo C, Castiglia M, Hong D, Alessandro R, Mertens I, Baggerman G, Zwaenepoel K, Gil-Bazo I, Passiglia F, Carreca AP, Taverna S, Vento R, Santini D, Peeters M, Russo A, Pauwels P. Liquid biopsies in lung cancer: the new ambrosia of researchers. Biochim Biophys Acta. 2014 Dec;1846(2):539-46. doi: 10.1016/j.bbcan.2014.10.001. Epub 2014 Oct 16. Review. Erratum in: Biochim Biophys Acta. 2015 Jan; 1855(1):17. Santini, Daniele [added]. — View Citation

Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219. — View Citation

Yu SC, Lee SW, Jiang P, Leung TY, Chan KC, Chiu RW, Lo YM. High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing. Clin Chem. 2013 Aug;59(8):1228-37. doi: 10.1373/clinchem.2013.203679. Epub 2013 Apr 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	prediction accuracy of survival rate	We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 5 year survival rate of patients is the primary endpoint	through study completion, an average of 5 years
Primary	prediction accuracy of recurrent rate	We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 3 year recurrent rate of patients is the primary endpoint	through study completion, an average of 3 years
Secondary	Mutation Consistency of tissue and blood sample	We do NGS sequencing of both the tissue sample and blood sample of the CRC patients. The gene mutation data will be analysis, and the percentage of same and different mutation of tissue and blood sample will be reported.	through study completion, an average of 3 years