ctDNA as a Prognostic Marker for Postoperative Relapse in Early and Intermediate Stage Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Circulating Tumor DNA as a Prognostic Marker for Postoperative Relapse in Early and Intermediate Stage Colorectal Cancer:A Prospective, Multicenter,Observational, Single-Blinded Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03312374
• Other study ID #: CTDNA-CRC
• Status: Recruiting
• Start date: August 1, 2017
• Est. completion date: March 30, 2020

Study information

• Verified date: February 2019
• 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 monitoring the serum ctDNA mutational profile using NGS, the present clinical trial aims to elucidate the correlation between the postoperative ctDNA status and the prognosis of patients with early and intermediate-stage colorectal cancer, and explore the possibility of clinical utility of serum ctDNA as a clinical index to predict postoperative relapse.

Description:

Colorectal cancer (CRC), as one of the common malignant tumors with high mobidity and mortality, is a major health threat in China.Surgical resection is the conventional treatment for early and intermediate stageCRC, however, it is not curative and postoperative recurrenceremains a clinical dilemma.Early detection of recurrence by serum tumor biomarkers and Computed Tomography (CT) during follow-up can improve the overall survival of patients with surgical resection. Nevertheless, thecurrently available tumor biomarkers have limited sensitivity and specificity, and CT is associated with radiation exposure. Therefore, there is a need for a more effective and feasible methodfor the prediction of postoperative recurrence.

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. UsingNext Generation Sequencing (NGS),Newman et al. have shown that the serum level of ctDNA was correlated withtumor progress and prognosis in NSCLC. Isaac et al. demonstrated the postoperativectDNA 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.

By monitoring the serum ctDNA mutational profile using NGS, the present clinical trial aims to elucidate the correlation between the postoperative ctDNA status and the prognosis of patients with early and intermediate-stage colorectal cancer, and explore the possibility of clinical utility of serum ctDNA as a clinical index to predict postoperative relapse.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: March 30, 2020
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female = 18 years of age on the day of signing informed consent.

2. Patients must have histologically confirmed stage II/IIIcolorectal cancer.

3. Patients need to receive surgical resection.

4. Patients must have a performance status of =1 on the ECOG Performance Scale.

5. Patients must have survival of > 12 months after the index date

6. Written informed consent must be obtained from patient or patient's legal representative and ability for patient to comply with the requirements of the study.

Exclusion Criteria:

1. Patients received adjuvant treatment prior to the surgical resection.

2. Patients received blood transfusion two weeks before or during the surgical resection.

3. Patients who are positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C.

4. Patients who are pregnant.

5. Patients who are alcoholic or drug abusers.

6. Patients with a history or current evidence of any condition or abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the Investigator.

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 (3)

Lead Sponsor	Collaborator
Sun Yat-sen University	Fudan University, Zhejiang 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. S — 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, Br — 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 Ma — 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 B — 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, Vogelste — 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	Disease Free Survival	The primary endpoint for this study is Disease Free Survival (DFS), which will be assessed using RECIST version 1.1.	through study completion, an average of 2 years