ctDNA Monitoring to Predict the Efficacy of TNT for Rectal Cancer

NCT06589388 | Recruiting

• 1 other identifier: GS_ZTR
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective observational study with three primary objectives: Objective 1: Evaluate the detection rate and changes in circulating tumor DNA (ctDNA) levels in blood samples from colorectal cancer patients before, during, and after total neoadjuvant therapy (TNT). Determine the detection rate and change of CtDNA in blood samples of cancer patients before, during, and after TNT then assess changes in ctDNA expression within the study population during treatment.

• Determine the ctDNA positivity rate before treatment.
• Determine the ctDNA positivity rate during TNT.
• Determine the ctDNA positivity rate after TNT and assess ctDNA level changes during treatment. Objective 2: Investigate the relationship between ctDNA expression and MRI/CT scan imaging with the pathological complete response (pCR) to neoadjuvant therapy :
• Correlation between ctDNA detection and pCR/TRG/NAR score. Calculate the Positive Prediction Value - PPV, Negative Prediction Value - NPV of ctDNA,
• Correlation between MRI/CT scan imaging and pCR. Calculate the PPV and NPV of MRI/CT scan
• Combination of ctDNA detection and MRI/CT scan imaging to predict pCR. Calculate the PPV and NPV of the combined markers. Objective 3: Evaluate the relationship between post-TNT ctDNA expression and disease-free survival in colorectal cancer patients.

Conditions

Rectal Cancer; Rectal Cancer Stage II; Rectal Cancer Stage III

Keywords

liquid biopsy; circulating tumor DNA; Vietnam; total neoadjuvant therapy

Outcome Measures

Primary Outcomes (3)

• To investigate the detection rate and change of ctDNA in blood samples of rectal cancer patients during total neoadjuvant therapy

  Determine the detection rate and change of CtDNA in blood samples of cancer patients before, during and after total neoadjuvant therapy and assess changes in ctDNA expression within the study population during treatment. * Determine the ctDNA positivity rate before treatment. * Determine the ctDNA positivity rate during total neoadjuvant therapy TNT. * Determine the ctDNA positivity rate after TNT and assess ctDNA level changes during treatment.

  12 months

• To investigate the relationship between ctDNA expression and MRI/CT scan imaging with pCR response in total neoadjuvant therapy (TNT)

  * To investigate the prediction value of ctDNA to pathological complete response (pCR) in TNT: Calculate the percentage PPV, NPV of ctDNA to pCR * To investigate the prediction value of MRI/CT results to pCR in TNT: Calculate the percentage PPV, NPV of MRI/CT scan (RECIST 1.1) to pCR * To investigate the prediction value of MRI/CT results combined ctDNA results to pCR in TNT: Calculate the percentage PPV, NPV of MRI/CT combined ctDNA to pCR

  6 months

• Evaluate the relationship between post-TNT ctDNA expression and disease-free survival in colorectal cancer patients in 2 years

  Create a Kaplan-Meier curve to estimate the disease-free survival of two years according to the after-treatment ctDNA status of patients.

  24 months

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population consists of patients aged 18 years and older, diagnosed with stage II-III rectal cancer, and indicated for total neoadjuvant chemotherapy. Participants must meet all inclusion criteria and no exclusion criteria. Recruitment will take place at 175 Military Hospital, Nguyen Tri Phuong Hospital, and 108 Military Center Hospital.

You may qualify if:

• years and older, both genders
• Patients are diagnosed with stage II-III rectal cancer and indicated for total neoadjuvant therapy
• Biopsy FFPE sample is available at the time of diagnosis
• Patients consented to participate in the study

You may not qualify if:

• Stage I rectal cancer, recurrent or metastatic cancer
• Other cancer metastasis to the rectum
• Patients are indicated for chemoradiation therapy only
• Have been or are being treated for cancer
• Patients do not agree to participate in the studies.

Sponsors & Collaborators

• Gene Solutions: lead

Study Sites (1)

Medical Genetics Institute

Ho Chi Minh City, Vietnam

RECRUITING

Related Publications (12)

• Kim MJ, Lee DW, Kang HC, Park JW, Ryoo SB, Han SW, Kim KS, Chie EK, Oh JH, Jeong WK, Kim BH, Nam EM, Jeong SY. Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial. BMC Cancer. 2023 Aug 8;23(1):734. doi: 10.1186/s12885-023-11177-7.

  PMID: 37553666 BACKGROUND

• Johnson GGRJ, Park J, Helewa RM, Goldenberg BA, Nashed M, Hyun E. Total neoadjuvant therapy for rectal cancer: a guide for surgeons. Can J Surg. 2023 Apr 21;66(2):E196-E201. doi: 10.1503/cjs.005822. Print 2023 Mar-Apr.

  PMID: 37085291 BACKGROUND

• Lopez-Campos F, Martin-Martin M, Fornell-Perez R, Garcia-Perez JC, Die-Trill J, Fuentes-Mateos R, Lopez-Duran S, Dominguez-Rullan J, Ferreiro R, Riquelme-Oliveira A, Hervas-Moron A, Counago F. Watch and wait approach in rectal cancer: Current controversies and future directions. World J Gastroenterol. 2020 Aug 7;26(29):4218-4239. doi: 10.3748/wjg.v26.i29.4218.

  PMID: 32848330 BACKGROUND

• Li LH, Chen ZF, Wang XF, Liu X, Jiang WZ, Zhuo SM, Jiang LW, Guan GX, Chen JX. Monitoring neoadjuvant therapy responses in rectal cancer using multimodal nonlinear optical microscopy. Oncotarget. 2017 Nov 3;8(63):107323-107333. doi: 10.18632/oncotarget.22366. eCollection 2017 Dec 5.

  PMID: 29291032 BACKGROUND

• Feeney G, Sehgal R, Sheehan M, Hogan A, Regan M, Joyce M, Kerin M. Neoadjuvant radiotherapy for rectal cancer management. World J Gastroenterol. 2019 Sep 7;25(33):4850-4869. doi: 10.3748/wjg.v25.i33.4850.

  PMID: 31543678 BACKGROUND

• Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rodel C, Cervantes A, Arnold D; ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. No abstract available.

  PMID: 28881920 BACKGROUND

• Hu H, Huang J, Lan P, Wang L, Huang M, Wang J, Deng Y. CEA clearance pattern as a predictor of tumor response to neoadjuvant treatment in rectal cancer: a post-hoc analysis of FOWARC trial. BMC Cancer. 2018 Nov 20;18(1):1145. doi: 10.1186/s12885-018-4997-y.

  PMID: 30458734 BACKGROUND

• Yan YY, Guo QR, Wang FH, Adhikari R, Zhu ZY, Zhang HY, Zhou WM, Yu H, Li JQ, Zhang JY. Cell-Free DNA: Hope and Potential Application in Cancer. Front Cell Dev Biol. 2021 Feb 22;9:639233. doi: 10.3389/fcell.2021.639233. eCollection 2021.

  PMID: 33693004 BACKGROUND

• McDuff SGR, Hardiman KM, Ulintz PJ, Parikh AR, Zheng H, Kim DW, Lennerz JK, Hazar-Rethinam M, Van Seventer EE, Fetter IJ, Nadres B, Eyler CE, Ryan DP, Weekes CD, Clark JW, Cusack JC, Goyal L, Zhu AX, Wo JY, Blaszkowsky LS, Allen J, Corcoran RB, Hong TS. Circulating Tumor DNA Predicts Pathologic and Clinical Outcomes Following Neoadjuvant Chemoradiation and Surgery for Patients With Locally Advanced Rectal Cancer. JCO Precis Oncol. 2021 Jan 12;5:PO.20.00220. doi: 10.1200/PO.20.00220. eCollection 2021.

  PMID: 34250394 BACKGROUND

• Dizdarevic E, Hansen TF, Jakobsen A. The Prognostic Importance of ctDNA in Rectal Cancer: A Critical Reappraisal. Cancers (Basel). 2022 Apr 30;14(9):2252. doi: 10.3390/cancers14092252.

  PMID: 35565381 BACKGROUND

• Nguyen Hoang VA, Nguyen ST, Nguyen TV, Pham TH, Doan PL, Nguyen Thi NT, Nguyen ML, Dinh TC, Pham DH, Nguyen NM, Nguyen DS, Nguyen DQ, Lu YT, Do TTT, Truong DK, Phan MD, Nguyen HN, Giang H, Tu LN. Genetic landscape and personalized tracking of tumor mutations in Vietnamese women with breast cancer. Mol Oncol. 2023 Apr;17(4):598-610. doi: 10.1002/1878-0261.13356. Epub 2023 Jan 15.

  PMID: 36495126 BACKGROUND

• Nguyen HT, Nguyen TV, Nguyen Hoang VA, Tran DH, Le Trinh NA, Le MT, Nguyen Tran TA, Pham TH, Dinh TC, Nguyen TS, Nguyen The KC, Mai H, Chu MT, Pham DH, Nguyen XC, Ngo Ha TM, Nguyen DS, Nguyen DQ, Lu YT, Do Thi TT, Truong DK, Nguyen QT, Nguyen HN, Giang H, Tu LN. Tumor genomic profiling and personalized tracking of circulating tumor DNA in Vietnamese colorectal cancer patients. Front Oncol. 2022 Dec 12;12:1069296. doi: 10.3389/fonc.2022.1069296. eCollection 2022.

  PMID: 36578946 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

The 1st samples are collected from participants of Rectal cancer, phase II-III. They will be processed and analyzed to determine the detection rate of ctDNA in the blood samples before total neoadjuvant chemotherapy. The 2nd and 3rd samples collected from participants will be processed and analyzed to determine the change of ctDNA in the blood samples during and after total neoadjuvant therapy.

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Sinh D Nguyen, PhD

  Medical Genetics Institude

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lan NL Tu, PhD

CONTACT

+84888843489; lantu@genesolutions.vn

Van T Phan, MSc

CONTACT

+84908145990; vanphan@genesolutions.vn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: September 19, 2024
• Study Start: May 21, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Dec 2027
• Access Criteria: GS\ ZTR\ ctDNA for Rectal Cancer

Locations

VN (1)