Circulating Tumor DNA-guided Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer
NCT ID: NCT05601505
Last Updated: 2024-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
470 participants
INTERVENTIONAL
2023-02-03
2026-11-01
Brief Summary
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Detailed Description
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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 demonstrated that ctDNA is an effective marker of tumor burden in real time and for the first time identified baseline ctDNA mutation frequency before nCRT as an independent prognostic factor for recent LARC recurrence and metastasis. This suggests that patients with different tumor burden according to baseline ctDNA mutation frequency should be given neoadjuvant therapy with corresponding intensity, in order to improve systemic disease control in patients with high risk of recurrence and metastasis, and to avoid overtreatment in patients with low risk.
In conclusion, 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. With the development of this study, several precision medicine research results obtained by our research group will be expected to be translated into clinical practice as soon as possible, which will improve the efficacy of LARC patients, reduce the rate of adverse reactions, and ultimately promote the improvement of the treatment level of rectal cancer and the more reasonable use of public medical resources.
The patients with locally advanced rectal cancer staged as cT3-4N0/cTanyN+ will be included in this study. Patients will be randomized into two groups, the experimental group will receive different strategies after next generation sequencing of tumor tissue and IMC, those with MSI-H or TMB-H will be advised to receive immune therapy, and the others will be arranged to randomly receive NCRT (baseline VAF\<0.5%) or total neoadjuvant therapy (TNT) (baseline VAF≥0.5% or a positive post-CRT ctDNA) according to the VAF value of ctDNA; the control group will receive modified NCRT only.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Traditional neoadjuvant chemoradiotherapy group
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
No interventions assigned to this group
ctDNA-guided neoadjuvant treatment group
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.
circulating tumor DNA
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.
Interventions
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circulating tumor DNA
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.
Eligibility Criteria
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Inclusion Criteria
2. ECOG score 0-2;
3. Rectal adenocarcinoma confirmed by pathology;
4. The lower margin of the tumor was less than 12cm from the anal margin;
5. Patients with clinical stage cT3-4N0M0 or cTanyN+M0;
6. Newly treated patients who have not received treatment including radiotherapy, chemotherapy and surgery;
7. Liver, kidney and other organs have good function and can tolerate radiotherapy, chemotherapy and surgery;
8. Patients and family members can understand the study protocol, voluntarily participate in the study and sign informed consent.
Exclusion Criteria
2. Patients with multiple primary colorectal cancers;
3. 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;
4. Complicated with intestinal obstruction, intestinal perforation, gastrointestinal bleeding and other patients requiring emergency surgery;
5. pregnant or lactating women;
6. Patients with a history of severe mental illness, immune disease, hormone medication;
7. Patients contraindicated by MRI examination, chemoradiotherapy, immunotherapy or surgery;
8. Participated in other clinical researchers in the past 3 months;
9. Any other circumstances that the investigator considers inappropriate for inclusion.
18 Years
75 Years
ALL
No
Sponsors
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Peking Union Medical College Hospital
OTHER
Responsible Party
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Locations
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Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences,
Beijing, Beijing Municipality, China
Countries
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Central Contacts
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Facility Contacts
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Lin guole, doctor
Role: primary
References
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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.
Other Identifiers
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2022-PUMCH-C-005
Identifier Type: -
Identifier Source: org_study_id