Circulating Tumor DNA-guided Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer

NCT05601505 | Recruiting Phase 2 DMC

• 1 other identifier: 2022-PUMCH-C-005
• Study Type: interventional
• Target: 470
• Locations: 1 country
• Sites: 1

Brief Summary

Rectal cancer still remains one of the most popular tumors, however, distance metastasis still remains as high as 30% and the long-term survival outcomes are still unsatisfying. The recent conception of total neoadjuvant therapy and immune therapy is becoming popular and the oncologic effects are encouraging, especially in terms of circulating tumor DNA (ctDNA), the prognostic value of ctDNA has been demonstrated by our prior study. This study will carry out accurate ctDNA-guided neoadjuvant therapy on the basis of previous studies of the research group, and give appropriate treatment plans and treatment intensity to patients with different disease degrees. At the same time, combined with the latest progress in clinical diagnosis and treatment, the potential beneficiaries of immunotherapy were screened scientifically, and the combined immunotherapy was implemented accordingly.

Conditions

Locally Advanced Rectal Carcinoma; Circulating Tumor DNA

Keywords

Locally advanced rectal cancer; circulating tumor DNA; Neoadjuvant chemoradiotherapy; Total neoadjuvant therapy; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• two-year disease-related treatment failure, 2y-DrTF

  the incidence of any of the following events occurring after treatment: identification of distant metastasis or progression to unresectable disease before surgery, non-radical resection of the primary tumour, local recurrence or distant metastasis after radical surgery, new primary colorectal tumour, or treatment-related death.

  2 years

Secondary Outcomes (7)

• Time to recurrence, TTR

  2 years

• Two-year overall survival, 2yOS

  2 years

• two-year disease-free survival (2yDFS)

  2 years

• clinical complete response (cCR) and near complete response (ncCR) rate

  up to 1 year

• pathologically complete response (pCR) rate

  up to 1 year

Study Arms (2)

Traditional neoadjuvant chemoradiotherapy group

NO INTERVENTION

Eligible patients randomized into arm A will receive traditional neoadjuvant chemoradiotherapy, including long-course radiotherapy with a total number of 45-50.4Gy in 25-28 fractions, and with concurrent 3 times of oral capecitabine, the strategies of capecitabine are: During radiotherapy: capecitabine 1650mg/m2/d, orally administered twice a day, d1-d14, every 3 weeks as a course; During the non-radiotherapy period: capecitabine 2000mg/m2/d, orally administered twice daily, d1-d14, every 3 weeks as a course

ctDNA-guided neoadjuvant treatment group

EXPERIMENTAL

After sequencing tumor tissue, those with MSI-H/TMB-H or POLD/POLE2 mutation willed be arranged to receive immune therapy following NCRT，Terelizumab，200mg. The others are arranged to randomly receive TNT (VAF\>0.4%) or NCRT (VAF\<0.4%) according to VAF value by the level of ctDNA. TNT： Long course radiotherapy combined with 2 courses of single-agent capecitabine chemotherapy → 6 courses of CapeOX (Capecitabine 2000mg/m2/ day, twice orally, d1-14; Oxaliplatin 100-130mg/m2, intravenous infusion, d1; Every 3 weeks for a course of treatment.) chemotherapy was performed 2 to 3 weeks after the end of chemotherapy.

Other: circulating tumor DNA

Interventions

circulating tumor DNA OTHER

This study will further testify the prognostic value of ctDNA in the treatment term of locally advanced rectal cancer, the higher the VAF value, the higher the risk of recurrence and metastasis.

ctDNA-guided neoadjuvant treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-75 years;
• ECOG score 0-2;
• Rectal adenocarcinoma confirmed by pathology;
• The lower margin of the tumor was less than 12cm from the anal margin;
• Patients with clinical stage cT3-4N0M0 or cTanyN+M0;
• Newly treated patients who have not received treatment including radiotherapy, chemotherapy and surgery;
• Liver, kidney and other organs have good function and can tolerate radiotherapy, chemotherapy and surgery;
• Patients and family members can understand the study protocol, voluntarily participate in the study and sign informed consent.

You may not qualify if:

• ECOG score \> 2;
• Patients with multiple primary colorectal cancers;
• A history of other malignant tumors (other than cured basal cell carcinoma, cervical carcinoma in situ, surgically treated localized prostate cancer, or surgically resected breast ductal carcinoma in situ) within the past 5 years;
• Complicated with intestinal obstruction, intestinal perforation, gastrointestinal bleeding and other patients requiring emergency surgery;
• pregnant or lactating women;
• Patients with a history of severe mental illness, immune disease, hormone medication;
• Patients contraindicated by MRI examination, chemoradiotherapy, immunotherapy or surgery;
• Participated in other clinical researchers in the past 3 months;

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences,

Beijing, Beijing Municipality, 100005, China

RECRUITING

Related Publications (2)

• Zhang X, Zhou J, Geng J, Li Y, Huang F, Shu W, Fu W, Zhou X, Wu G, Jia W, Cui J, Wang Z, Han J, Shi B, Li L, Rui J, Xue H, Hu K, Xu T, Chen W, Lu J, Yao H, Liu Q, Lin G. Feasibility of ctDNA-guided precision neoadjuvant therapy in locally advanced rectal cancer: Insights from the ongoing CINTS-R trial. Eur J Cancer. 2026 Feb 5;234:116193. doi: 10.1016/j.ejca.2025.116193. Epub 2025 Dec 18.

  PMID: 41435753 DERIVED

• Zhou J, Zhang X, Liu Q, Li Y, Wu G, Fu W, Yao H, Wang Z, Xue H, Xu T, Chen W, Lu J, Zhang G, Wu B, An Y, Qiu X, Xiao Y, Lin G. Rationale and design of a multicentre randomised controlled trial on circulating tumour DNA-guided neoadjuvant treatment strategy for locally advanced rectal cancer (CINTS-R). BMJ Open. 2025 Feb 2;15(1):e090765. doi: 10.1136/bmjopen-2024-090765.

  PMID: 39894522 DERIVED

MeSH Terms

Interventions

Circulating Tumor DNA

Intervention Hierarchy (Ancestors)

Cell-Free Nucleic Acids; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; DNA, Neoplasm; DNA

Central Study Contacts

Lin guole, Doctor

CONTACT

13801081483; linguole@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 1, 2022
• Study Start: February 3, 2023
• Primary Completion: October 31, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The datasets analyzed during the current study and other supporting information will be available no earlier than 1 year following the date of publication.
• Access Criteria: IPD and supporting information can be accessed based on reasonable request by contacting the corresponding author.

Locations

CN (1)