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

Официальное название

Circulating Tumor DNA-guided Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer --- a Multicenter Randomized Controlled Trial (CINTS-R)

Обзор

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.

Подробное описание

Rectal cancer still remains one of the most popular tumors, a multidisciplinary approach including neoadjuvant chemoradiotherapy, total mesorectal excision and adjuvant chemotherapy has resulted a satisfying oncologic outcome in terms of reducing local recurrence and improving local control of disease for the treatment of rectal cancer, however, distance metastasis still remains as high as 30% and the long-term survival outcomes is 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 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.

Вмешательства

• Другое 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.

Первичные конечные точки

• two-year disease-related treatment failure, 2y-DrTF [Срок оценки: 2 years]

Вторичные конечные точки (7)

• Time to recurrence, TTR [Срок оценки: 2 years]
• Two-year overall survival, 2yOS [Срок оценки: 2 years]
• two-year disease-free survival (2yDFS) [Срок оценки: 2 years]
• clinical complete response (cCR) and near complete response (ncCR) rate [Срок оценки: up to 1 year]
• pathologically complete response (pCR) rate [Срок оценки: up to 1 year]
• pathological tumour regression grade (pTRG) [Срок оценки: up to 1 year]
• Quality of life assessment (QoL) [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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;
• Any other circumstances that the investigator considers inappropriate for inclusion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical — Пекин

Публикации

• 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
• 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

Идентификаторы

NCT: NCT05601505 · 2022-PUMCH-C-005

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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