Clinical trial NCT05969938: Predicting the Efficacy and Prognosis of Rectal Cancer Patients Based on ctDNA-MRD Technology
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rectal Adenocarcinoma
Circulating Tumor DNA
Minimal Residual Disease
Neoadjuvant Chemoradiotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Haplox Biotechnology Co., Ltd.
First posted: 2023-08-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study intends to include 50 patients with stage II-III rectal cancer who plan to receive neoadjuvant chemoradiotherapy between the ages of 18-75 years old.

Brief 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.

Detailed 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 ).

Eligibility criteria: 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. -

Primary outcomes:
measure: Area under the ROC curve (AUC) of the MRD biomarker
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Local recurrence-free survival（LRFS）
timeFrame: From date of radical surgery to local recurrence or death due to disease progression，assessed up to 60 months.
measure: Distant metastases-free survival（DMFS）
timeFrame: From date of the beginning of neoadjuvant chemoradiotherapy to disease metastasis or death due to any cause,assessed up to 60 months.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: WeiWei Xiao
state: Guangdong
Study officials:
References:
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.
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.
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.
citation: 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.
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.