Node-Sparing Short-Course Radiation with CAPOX and Sintilimab for MSS Locally Advanced Colon Cancer: a Randomized, Prospective, Multicenter Study
NCT ID: NCT06594692
Last Updated: 2024-09-19
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
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
NOT_YET_RECRUITING
PHASE2
140 participants
INTERVENTIONAL
2024-10-31
2026-09-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction
NCT04263870
Neoadjuvant Tislelizumab With Chemotherapy for the Treatment of MSS Colon Cancer
NCT06124378
A Single-arm, Phase II Exploratory Study of Sintilimab in Combination With Chemoradiotherapy in Elderly Patients With Locally Advanced Gastric Cancer
NCT06555471
A Study on the Combination of Sintilimab, Ramucirumab and Chemotherapy for First-line Treatment of Gastric Cancer With Liver Metastasis
NCT06564298
Safety and Efficacy of Sintilimab in Combination With Chemoradiothrapy Followed by D2 Surgical Resection in Patients With Advanced Gastric Cancer With Retroperitoneal Lymph Node Metastasis
NCT05002686
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Neoadjuvant chemotherapy, which is administered before surgery, offers several theoretical advantages, including shrinking the primary tumor to improve surgical resection rates, reducing intraoperative tumor cell spread, and eliminating micrometastases and subclinical lesions to lower the risk of postoperative metastasis. However, data on neoadjuvant chemotherapy for locally advanced colon cancer remains limited. The FOxTROT study found that preoperative neoadjuvant chemotherapy significantly reduced the 2-year recurrence rate for locally advanced colon cancer, achieved tumor downstaging, and provided a 4% pathological complete response (pCR) rate. This study also demonstrated a strong correlation between pathological response to neoadjuvant therapy and recurrence risk, with patients achieving pCR or major pathological response (mPR) having significantly lower recurrence rates.
Recent studies have shown that combining immunotherapy with radiotherapy has a synergistic effect, even in MSS-type colorectal cancer patients. Radiotherapy can induce immunogenic cell death, releasing tumor-associated antigens and enhancing the function of dendritic cells, thereby increasing T-cell infiltration. Moreover, chemotherapy can alter the tumor microenvironment, promote angiogenesis, and improve oxygen distribution, further enhancing the efficacy of radiotherapy. One prospective phase II clinical trial involving locally advanced rectal cancer patients showed promising results, with a pCR rate of 46.2% in patients with proficient mismatch repair (pMMR), suggesting a favorable response to neoadjuvant therapy.
Lymph nodes, as secondary lymphoid organs, play a crucial role in tumor diagnosis and treatment. Recent preclinical studies have shown that tumor-draining lymph nodes (TDLNs) are essential in antigen activation and effector T-cell differentiation. On the other hand, tertiary lymphoid structures (TLS), which are organized immune cell aggregates formed in non-lymphoid tissues, have been associated with improved prognosis in cancer patients. However, the role of TDLNs in immunotherapy remains underexplored.
Based on these findings, the research team hypothesizes that tumor-draining lymph nodes play a positive role in immunotherapy response, and sparing these nodes during radiotherapy may enhance the efficacy of immunotherapy for MSS-type colorectal cancer. The team previously conducted a phase II clinical study (NCT04503694) investigating the safety and efficacy of node-sparing short-course radiotherapy combined with CAPOX chemotherapy and PD-1 inhibitors in MSS-type locally advanced rectal cancer. Results showed a 100% response rate to neoadjuvant therapy, with a pCR rate of 78.8% and a major pathological response (mPR) rate of 91%, while maintaining a high rate of organ preservation.
Given the high recurrence rates and treatment challenges associated with locally advanced colon cancer, and building on the promising results of previous studies, the research team intends to conduct the mRCAT-C study. This study aims to explore the clinical efficacy and safety of a node-sparing short-course radiotherapy combined with immunotherapy as a neoadjuvant treatment for MSS-type locally advanced colon cancer.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab
Intervention Procedure:
1. Radiotherapy: Short-course radiotherapy is administered, with a total dose of 25Gy (5Gy per session for 5 sessions) targeting the primary tumor.
2. Chemotherapy and Immunotherapy: On the 8th day after the start of radiotherapy, CAPOX chemotherapy combined with Sintilimab is initiated for 4 cycles.
3. Surgery: One week after the completion of chemotherapy and immunotherapy, patients will undergo radical total mesorectal excision surgery.
4. Postoperative Adjuvant Chemotherapy: Starting 3-4 weeks after surgery, patients will resume CAPOX chemotherapy for an additional 4 cycles as adjuvant treatment.
Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab
Radiotherapy Protocol:
Short-course radiotherapy using three-dimensional conformal or intensity-modulated radiation therapy techniques. The radiation field will be limited to the tumor bed of the primary colon lesion, excluding surrounding draining lymph nodes and enlarged lymph nodes. The dose is fractionated as 5Gy per fraction, for a total of 25Gy over 5 fractions. Titanium clips will be placed on the proximal and distal ends of the colonic lesion via colonoscopy to guide radiation therapy positioning.
Chemotherapy Protocol (CAPOX Regimen):
1. Oxaliplatin: 130 mg/m², administered intravenously (ivgtt), on day 1 (d1).
2. Capecitabine: 1000 mg/m², orally (po), twice daily (bid), from day 1 to day 14 (d1-14).
Immunotherapy Protocol:
During preoperative treatment, Sintilimab (immune checkpoint inhibitor) will be administered concurrently with each chemotherapy cycle.
Preoperative CAPOX Regimen as Neoadjuvant Therapy
Intervention Procedure:
1. Chemotherapy: Administer CAPOX chemotherapy for 4 cycles.
2. Surgery: One week after the completion of chemotherapy, patients will undergo radical total mesorectal excision surgery.
3. Postoperative Adjuvant Chemotherapy: Starting 3-4 weeks after surgery, patients will resume CAPOX chemotherapy for an additional 4 cycles as adjuvant treatment.
CAPOX Chemotherapy
Participants will receive 4 cycles of CAPOX chemotherapy followed by radical total mesorectal excision surgery, and then 4 additional cycles of postoperative CAPOX chemotherapy.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab
Radiotherapy Protocol:
Short-course radiotherapy using three-dimensional conformal or intensity-modulated radiation therapy techniques. The radiation field will be limited to the tumor bed of the primary colon lesion, excluding surrounding draining lymph nodes and enlarged lymph nodes. The dose is fractionated as 5Gy per fraction, for a total of 25Gy over 5 fractions. Titanium clips will be placed on the proximal and distal ends of the colonic lesion via colonoscopy to guide radiation therapy positioning.
Chemotherapy Protocol (CAPOX Regimen):
1. Oxaliplatin: 130 mg/m², administered intravenously (ivgtt), on day 1 (d1).
2. Capecitabine: 1000 mg/m², orally (po), twice daily (bid), from day 1 to day 14 (d1-14).
Immunotherapy Protocol:
During preoperative treatment, Sintilimab (immune checkpoint inhibitor) will be administered concurrently with each chemotherapy cycle.
CAPOX Chemotherapy
Participants will receive 4 cycles of CAPOX chemotherapy followed by radical total mesorectal excision surgery, and then 4 additional cycles of postoperative CAPOX chemotherapy.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
4\. Histologically diagnosed adenocarcinoma; genetic testing indicates MSI-L or MSS, or immunohistochemistry from tumor biopsy shows pMMR (all four proteins-MSH1, MSH2, MSH6, and PMS2-are positive).
5\. Clinical staging by enhanced abdominal CT evaluates as cT3-4N0-2M0. 6. ECOG performance status score of 0-1. 7. No prior treatment with anti-tumor, immunotherapy, or abdominal radiation therapy before enrollment.
8\. Blood test results (without transfusion within 14 days and no use of granulocyte colony-stimulating factor or other hematopoietic stimulators within 7 days before the lab test):
1. White blood cell count ≥ 3.5 × 10\^9/L, absolute neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, hemoglobin concentration ≥ 9 g/dL;
2. Liver function tests (bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 5 × ULN);
3. Renal function (serum creatinine ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50 mL/min);
4. Coagulation (INR ≤ 1.5 × ULN, PT and APTT ≤ 1.5 × ULN);
5. Thyroid function: TSH ≤ upper limit of normal (ULN); if abnormal, FT3 and FT4 levels must be evaluated, and if FT3 and FT4 are normal, the patient is eligible.
9\. Voluntary participation with a signed informed consent form.
Exclusion Criteria
5\. Known allergy to the study drug or any of its excipients. 6. Patients with any unstable systemic diseases, including but not limited to severe infections, uncontrolled diabetes, uncontrolled hypertension, unstable angina, cerebrovascular accidents or transient ischemic attacks, myocardial infarction, congestive heart failure, or severe illnesses requiring medication (such as arrhythmias, liver, kidney, or metabolic diseases) that are life-threatening.
7\. History of active autoimmune diseases requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within the last 2 years. Replacement therapies (e.g., thyroid hormone, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic treatments.
8\. Known history of HIV infection or acquired immunodeficiency syndrome (AIDS). 9. Receipt of any investigational drug (including immunotherapy) or participation in another interventional clinical study within 30 days before screening.
10\. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study; men or women unwilling to use effective contraception during the study.
11\. Vulnerable populations, including those with mental illness, cognitive impairment, or critically ill patients.
12\. Any other conditions deemed inappropriate for participation by the investigator.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Sir Run Run Shaw Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Zhangfa Song
Professor
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Sir Run Run Shaw Hospital, Zhejiang University
Hangzhou, China, China
Sir Run Run Shaw Hospital, Zhejiang University
Hangzhou, Zhejiang, China
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Role: primary
References
Explore related publications, articles, or registry entries linked to this study.
Wang Q, Zhong W, Shen X, Hao Z, Wan M, Yang X, An R, Zhu H, Cai H, Li T, Lv Y, Dong X, Chen G, Liu A, Du J. Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer. NPJ Precis Oncol. 2024 Mar 2;8(1):61. doi: 10.1038/s41698-024-00533-w.
Vanhersecke L, Brunet M, Guegan JP, Rey C, Bougouin A, Cousin S, Moulec SL, Besse B, Loriot Y, Larroquette M, Soubeyran I, Toulmonde M, Roubaud G, Pernot S, Cabart M, Chomy F, Lefevre C, Bourcier K, Kind M, Giglioli I, Sautes-Fridman C, Velasco V, Courgeon F, Oflazoglu E, Savina A, Marabelle A, Soria JC, Bellera C, Sofeu C, Bessede A, Fridman WH, Loarer FL, Italiano A. Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression. Nat Cancer. 2021 Aug;2(8):794-802. doi: 10.1038/s43018-021-00232-6. Epub 2021 Aug 12.
Rahim MK, Okholm TLH, Jones KB, McCarthy EE, Liu CC, Yee JL, Tamaki SJ, Marquez DM, Tenvooren I, Wai K, Cheung A, Davidson BR, Johri V, Samad B, O'Gorman WE, Krummel MF, van Zante A, Combes AJ, Angelo M, Fong L, Algazi AP, Ha P, Spitzer MH. Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell. 2023 Mar 16;186(6):1127-1143.e18. doi: 10.1016/j.cell.2023.02.021.
Zhang C, Zhang L, Xu T, Xue R, Yu L, Zhu Y, Wu Y, Zhang Q, Li D, Shen S, Tan D, Bai F, Zhang H. Mapping the spreading routes of lymphatic metastases in human colorectal cancer. Nat Commun. 2020 Apr 24;11(1):1993. doi: 10.1038/s41467-020-15886-6.
Lin Z, Cai M, Zhang P, Li G, Liu T, Li X, Cai K, Nie X, Wang J, Liu J, Liu H, Zhang W, Gao J, Wu C, Wang L, Fan J, Zhang L, Wang Z, Hou Z, Ma C, Yang K, Wu G, Tao K, Zhang T. Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer. J Immunother Cancer. 2021 Nov;9(11):e003554. doi: 10.1136/jitc-2021-003554.
Seo I, Lee HW, Byun SJ, Park JY, Min H, Lee SH, Lee JS, Kim S, Bae SU. Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer. J Immunother Cancer. 2021 Mar;9(3):e001610. doi: 10.1136/jitc-2020-001610.
Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, Monkhorst K, Baas P. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Sep 1;5(9):1276-1282. doi: 10.1001/jamaoncol.2019.1478.
Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May;23(5):659-670. doi: 10.1016/S1470-2045(22)00197-8. Epub 2022 Apr 12.
Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z, Yaeger R, Smith JJ, Rousseau B, Argiles G, Patel M, Desai A, Saltz LB, Widmar M, Iyer K, Zhang J, Gianino N, Crane C, Romesser PB, Pappou EP, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser MR, Schalper KA, Diaz LA Jr. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022 Jun 23;386(25):2363-2376. doi: 10.1056/NEJMoa2201445. Epub 2022 Jun 5.
Yuan Y, Xiao WW, Xie WH, Cai PQ, Wang QX, Chang H, Chen BQ, Zhou WH, Zeng ZF, Wu XJ, Liu Q, Li LR, Zhang R, Gao YH. Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection. BMC Cancer. 2021 Feb 19;21(1):179. doi: 10.1186/s12885-021-07894-6.
Chang H, Yu X, Xiao WW, Wang QX, Zhou WH, Zeng ZF, Ding PR, Li LR, Gao YH. Neoadjuvant chemoradiotherapy followed by surgery in patients with unresectable locally advanced colon cancer: a prospective observational study. Onco Targets Ther. 2018 Jan 17;11:409-418. doi: 10.2147/OTT.S150367. eCollection 2018.
Qiu B, Ding PR, Cai L, Xiao WW, Zeng ZF, Chen G, Lu ZH, Li LR, Wu XJ, Mirimanoff RO, Pan ZZ, Xu RH, Gao YH. Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer. Chin J Cancer. 2016 Jul 7;35(1):65. doi: 10.1186/s40880-016-0126-y.
Ludmir EB, Arya R, Wu Y, Palta M, Willett CG, Czito BG. Role of Adjuvant Radiotherapy in Locally Advanced Colonic Carcinoma in the Modern Chemotherapy Era. Ann Surg Oncol. 2016 Mar;23(3):856-62. doi: 10.1245/s10434-015-4907-3. Epub 2015 Oct 19.
Agas RAF, Co LBA, Sogono PG, Jacinto JCKM, Yu KKL, Jacomina LE, Bacorro WR, Sy Ortin TT. Assessing the Effect of Radiotherapy in Addition to Surgery in Colon Adenocarcinomas: a Systematic Review and Meta-analysis of Contemporary Evidence. J Gastrointest Cancer. 2020 Jun;51(2):445-460. doi: 10.1007/s12029-019-00300-2.
Fernandez LM, Sao Juliao GP, Figueiredo NL, Beets GL, van der Valk MJM, Bahadoer RR, Hilling DE, Meershoek-Klein Kranenbarg E, Roodvoets AGH, Renehan AG, van de Velde CJH, Habr-Gama A, Perez RO; International Watch & Wait Database Consortium. Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the International Watch & Wait Database: a retrospective, international, multicentre registry study. Lancet Oncol. 2021 Jan;22(1):43-50. doi: 10.1016/S1470-2045(20)30557-X. Epub 2020 Dec 11.
Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.
Hu H, Zhang J, Li Y, Wang X, Wang Z, Wang H, Kang L, Liu P, Lan P, Wu X, Zhen Y, Pei H, Huang Z, Zhang H, Chen W, Zeng Y, Lai J, Wei H, Huang X, Chen J, Chen J, Tao K, Xu Q, Peng X, Liang J, Cai G, Ding K, Ding Z, Hu M, Zhang W, Tang B, Hong C, Cao J, Huang Z, Cao W, Li F, Wang X, Wang C, Huang Y, Zhao Y, Cai Y, Ling J, Xie X, Wu Z, Shi L, Ling L, Liu H, Wang J, Huang M, Deng Y; OPTICAL study group. Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial. J Clin Oncol. 2024 Sep 1;42(25):2978-2988. doi: 10.1200/JCO.23.01889. Epub 2024 Apr 2.
Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, Palmer A, Seligmann J, Laurberg S, Murakami K, West N, Quirke P, Gray R; FOxTROT Collaborative Group. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023 Mar 10;41(8):1541-1552. doi: 10.1200/JCO.22.00046. Epub 2023 Jan 19.
Hu Z, Ding J, Ma Z, Sun R, Seoane JA, Scott Shaffer J, Suarez CJ, Berghoff AS, Cremolini C, Falcone A, Loupakis F, Birner P, Preusser M, Lenz HJ, Curtis C. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019 Jul;51(7):1113-1122. doi: 10.1038/s41588-019-0423-x. Epub 2019 Jun 17.
van der Bij GJ, Oosterling SJ, Beelen RH, Meijer S, Coffey JC, van Egmond M. The perioperative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer. Ann Surg. 2009 May;249(5):727-34. doi: 10.1097/SLA.0b013e3181a3ddbd.
Lin G, Feng Z, Liu H, Li Y, Nie Y, Liang Y, Li K. Mass screening for colorectal cancer in a population of two million older adults in Guangzhou, China. Sci Rep. 2019 Jul 18;9(1):10424. doi: 10.1038/s41598-019-46670-2.
Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. eCollection 2024 Mar.
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
mRCAT-C
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.