Predicting the Efficacy and Prognosis of Rectal Cancer Patients Based on ctDNA-MRD Technology

Minimal Residual Disease Clinical Trial

Official title:

Predicting the Efficacy and Prognosis of Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy Based on Circulating Tumor DNA-minimal Residual Disease Technology : A Prospective, Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05969938
• Other study ID #: B2023-239-01
• Status: Recruiting
• Start date: June 21, 2023
• Est. completion date: August 31, 2024

Study information

• Verified date: July 2023
• Source: Sun Yat-sen University
• Contact: WeiWei Xiao
• Phone: 8613710390520
• Email: xiaoww[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to study the performance of MRD monitoring in predicting the efficacy and prognosis of neoadjuvant therapy in patients with rectal cancer, and to explore the value of MRD detection in evaluating the prognosis of patients. In this prospective study, 50 patients with stage II-III rectal cancer who are planing to receive neoadjuvant chemoradiotherapy will be enrolled. The tumor tissue will be collected by colonoscopy before treatment and blood samples will be collected before treatment and during treatment.The whole blood samples will receive MRD detection. The change rate and clearance rate of MRD during treatment will be calculated, and will be associated with imaging efficacy evaluation, pathological efficacy evaluation,and prognosis, to determine the performance of MRD in predicting and judging the efficacy of neoadjuvant chemoradiotherapy and postoperative recurrence of rectal cancer.

Description:

This study is a prospective, observational study. It is expected to enroll 50 patients with newly diagnosed stage II-III rectal cancer.Before neoadjuvant chemoradiotherapy, tumor tissue will be collected by colonoscopy biopsy for WES and customized panel design, and peripheral blood samples will be collected for baseline MRD detection ( MRD1 ) and during neoadjuvant concurrent chemoradiotherapy ( MRD2-6 ) .Peripheral blood sample will be collected 3-4 weeks after radical surgery ( MRD7 ). For patients who achieved cCR after the end of neoadjuvant therapy and adopted the W & W ( watch and wait ) strategy, the sampling time point was 3 months after the start of watching and waiting ( MRD7 ).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 18-75

2. Rectal adenocarcinoma confirmed by pathology

3. The clinical stage is II-III.

4. Neoadjuvant chemoradiotherapy + radical surgery is planned ( cCR patients can choose to wait for observation ).

5. ECOG 0-1;

6. No distant metastasis ;

7. Main organ function is normal ;

8. signed informed consent and willing to accept long-term follow-up;

9. No anti-tumor treatment was received within 4 weeks before baseline sampling ;

10. Adequate ' colonoscopy ' tumor tissue samples can be provided for MRD customization, and sufficient whole blood samples need to be provided for baseline MRD detection.

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Exclusion Criteria:

1. unable to provide sufficient tissue / blood samples to meet the research needs ;

2. received radiotherapy, chemotherapy, or other targeted or immunotherapy before enrollment ;

3. Patients did not receive neoadjuvant therapy according to the original plan ;

4. Patients refused to accept genetic testing. -

Related Conditions & MeSH terms

• Circulating Tumor DNA
• Minimal Residual Disease
• Neoadjuvant Chemoradiotherapy
• Neoplasm, Residual
• Rectal Adenocarcinoma

Intervention

Diagnostic Test:
• MRD detection
Peripheral blood samples were collected for MRD detection before neoadjuvant chemoradiotherapy, during neoadjuvant chemoradiotherapy, and 3-4 weeks after radical surgery. For patients who achieved cCR after neoadjuvant therapy and adopted the W & W strategy, the sampling time point was 3 months after the start of watching and waiting.

Locations

Country	Name	City	State
China	WeiWei Xiao	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
WeiWei Xiao	Haplox Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (5)

Pazdirek F, Minarik M, Benesova L, Halkova T, Belsanova B, Macek M, Stepanek L, Hoch J. Monitoring of Early Changes of Circulating Tumor DNA in the Plasma of Rectal Cancer Patients Receiving Neoadjuvant Concomitant Chemoradiotherapy: Evaluation for Prognosis and Prediction of Therapeutic Response. Front Oncol. 2020 Jul 24;10:1028. doi: 10.3389/fonc.2020.01028. eCollection 2020. — View Citation

Scholer LV, Reinert T, Orntoft MW, Kassentoft CG, Arnadottir SS, Vang S, Nordentoft I, Knudsen M, Lamy P, Andreasen D, Mortensen FV, Knudsen AR, Stribolt K, Sivesgaard K, Mouritzen P, Nielsen HJ, Laurberg S, Orntoft TF, Andersen CL. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445. doi: 10.1158/1078-0432.CCR-17-0510. Epub 2017 Jun 9. — View Citation

Wang Y, Yang L, Bao H, Fan X, Xia F, Wan J, Shen L, Guan Y, Bao H, Wu X, Xu Y, Shao Y, Sun Y, Tong T, Li X, Xu Y, Cai S, Zhu J, Zhang Z. Utility of ctDNA in predicting response to neoadjuvant chemoradiotherapy and prognosis assessment in locally advanced rectal cancer: A prospective cohort study. PLoS Med. 2021 Aug 31;18(8):e1003741. doi: 10.1371/journal.pmed.1003741. eCollection 2021 Aug. — View Citation

Yang Y, Xu H, Chen G, Pan Y. Stratified Prognostic Value of Pathological Response to Preoperative Treatment in yp II/III Rectal Cancer. Front Oncol. 2021 Dec 16;11:795137. doi: 10.3389/fonc.2021.795137. eCollection 2021. — View Citation

Zhou J, Wang C, Lin G, Xiao Y, Jia W, Xiao G, Liu Q, Wu B, Wu A, Qiu H, Zhang F, Hu K, Xue H, Shen Z, Wang Z, Han J, Niu B, Xu Y, Yu Z, Yang L. Serial Circulating Tumor DNA in Predicting and Monitoring the Effect of Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer: A Prospective Multicenter Study. Clin Cancer Res. 2021 Jan 1;27(1):301-310. doi: 10.1158/1078-0432.CCR-20-2299. Epub 2020 Oct 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the ROC curve (AUC) of the MRD biomarker	The area under the ROC curve ( AUC ) of MRD	Baseline to 12 months
Secondary	Local recurrence-free survival(LRFS)	LRFS differences in patients with MRD clearance / decrease / increase	From date of radical surgery to local recurrence or death due to disease progression,assessed up to 60 months.
Secondary	Distant metastases-free survival(DMFS)	DMFS differences in patients with MRD clearance / decrease / increase	From date of the beginning of neoadjuvant chemoradiotherapy to disease metastasis or death due to any cause,assessed up to 60 months.