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| Name | Class |
|---|---|
| Southwest Hospital, China | OTHER |
| Xinqiao Hospital of Chongqing | OTHER |
| First Affiliated Hospital of Chongqing Medical University | OTHER |
| The Second Affiliated Hospital of Chongqing Medical University |
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The purpose of this clinical trial is to learn the safety and efficacy of HDAC inhibitors in combination with neoadjuvant immunochemotherapy compared to neoadjuvant therapy in the treatment of locally advanced colon cancer.
The main questions it aims to answer are:
Can HDAC inhibitors combined with neoadjuvant immunochemotherapy improve the rate of pCR and complete resection in patients? Are HDAC inhibitors combined with neoadjuvant immunochemotherapy safe and reliable? Does the combination of HDAC inhibitors and neoadjuvant immunochemotherapy achieve a better long-term prognosis than neoadjuvant therapy?
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chidamide + Tislelizumab + chemotherapy (CapeOX ) | Experimental | 4 cycles of combination therapy (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; tislelizumab, 200mg/m2 iv.gtt; Day1,4,8,11Chidamide 20 mg BIW,PO; Day1-Day14, capecitabine 850-1000mg/m2, BID, PO) |
|
| Neoadjuvant chemotherapy (CapeOX) | Active Comparator | 4 cycles Capeex (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chidamide + Tislelizumab + chemotherapy (CapeOX ) | Drug | Chidamide + Tislelizumab + chemotherapy (CapeOX regimen): 4 cycles of combination therapy (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; tislelizumab, 200mg/m2 iv.gtt; Day1,4,8,11Chidamide 20 mg BIW,PO; Day1-Day14, capecitabine 850-1000mg/m2, BID, PO) ï¼›After completing the surgery, Post-operation 4 cycles of Capeox |
| Measure | Description | Time Frame |
|---|---|---|
| pCR | pCR was defined as the absence, from surgical samples, of malignant cells in the primary site and regional lymph nodes | The pCR rate will be evaluated after surgery, an average of 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Disease-free survival | Defined as the time from randomization to relapse or death, whichever occurred first. | 3 years |
| Overall survival (OS) | Defined as the time from randomization to date of death due to any cause according to RECIST version 1.1 recorded in the time period between randomization and disease progression or death to any cause |
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Inclusion Criteria:
Exclusion Criteria:
History of previous allergy to monoclonal antibodies, any component of HDACi, and capecitabine;
Has received or is receiving any of the following treatments in the past:
Has any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
dMMR/MSI-H;
Presence of cardiac clinical symptoms or diseases that are not well controlled,
Severe infection (CTCAE > grade 2) within 4 weeks prior to the first use of study drug, with active tuberculosis infection found by medical history or CT examination,
Presence of active hepatitis B, hepatitis C 8.5 years of diagnosis of other malignant tumors, (adequately treated basal cell carcinoma of the skin or squamous cell skin cancer or carcinoma in situ of the cervix, etc., can be considered for enrollment);
9. Pregnant or lactating females; 10. As judged by the investigator, there are other factors that may lead to forced termination of the study, such as other serious diseases (including mental illnesses) requiring concomitant treatment, alcoholism, drug abuse, family or social factors, and factors that may affect the safety or compliance of the subject.
11. Have a history of immunodeficiency, including a positive HIV test, or have other acquired or congenital immunodeficiency disorders, or have a history of organ transplantation or allogeneic bone marrow transplantation;
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| fan li, PhD | Contact | 18696539200 | levinecq@163.com |
| Name | Affiliation | Role |
|---|---|---|
| fan Li, PhD | Third Military Medical University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Daping Hospital, Third Military Medical University | Recruiting | Chongqing | Chongqing Municipality | 400000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32702383 | Result | Argiles G, Tabernero J, Labianca R, Hochhauser D, Salazar R, Iveson T, Laurent-Puig P, Quirke P, Yoshino T, Taieb J, Martinelli E, Arnold D; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Oct;31(10):1291-1305. doi: 10.1016/j.annonc.2020.06.022. Epub 2020 Jul 20. No abstract available. | |
| 36657089 |
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| OTHER |
| Chongqing Medical University | OTHER |
| Chongqing University Cancer Hospital | OTHER |
| Chongqing General Hospital | OTHER |
| Chongqing Traditional Chinese Medicine Hospital | OTHER |
| Chongqing Shapingba District People's Hospital | UNKNOWN |
| Chongqing Seventh People's Hospital | UNKNOWN |
| Chongqing Renji Hospital, University of Chinese Academy of Sciences | OTHER_GOV |
| The 13th People's Hospital of Chongqing | UNKNOWN |
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|
| CapeOX | Drug | 4 cycles (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ) Post-operation 4 cycles of Capeox |
|
| 3 years |
| MPR | After neoadjuvant therapy, the percentage of residual viable tumor cells in the tumor bed ≤ 10%. Regardless of whether there are viable tumor cells left in the lymph nodes | From enrollment to 12 Weeks of treatment end |
| Curative resection | Curative resection defined as complete tumor resection with all margins being negative. | From enrollment to 12 Weeks of treatment end |
| ORR | Objective response is defined as a complete response (CR) or response (PR) according to RECIST v1.1 | From enrollment to 12 Weeks of treatment end |
| Down-staging of primary tumors | Down-staging of the resected tumour as measured by histopathological tumour diameter and stage according to the TNM staging system of AJCC (7th version). | From enrollment to 12 Weeks of treatment end |
| Postoperative complications | Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. | 3 years |
| Grade 3-4 adverse effects rate | Rate of chemotherapy andHDACI and immunotherapy related severe adverse events | From date of randomization until the date of death from any cause, assessed up to 3 years |
| Result |
| 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. |
| 38564700 | Result | 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. |
| 11171826 | Result | Michael-Robinson JM, Biemer-Huttmann A, Purdie DM, Walsh MD, Simms LA, Biden KG, Young JP, Leggett BA, Jass JR, Radford-Smith GL. Tumour infiltrating lymphocytes and apoptosis are independent features in colorectal cancer stratified according to microsatellite instability status. Gut. 2001 Mar;48(3):360-6. doi: 10.1136/gut.48.3.360. |
| 28596308 | Result | Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. doi: 10.1126/science.aan6733. Epub 2017 Jun 8. |
| 23432814 | Result | Jordaan G, Liao W, Sharma S. E-cadherin gene re-expression in chronic lymphocytic leukemia cells by HDAC inhibitors. BMC Cancer. 2013 Feb 25;13:88. doi: 10.1186/1471-2407-13-88. |
| 32391971 | Result | Shankar E, Pandey M, Verma S, Abbas A, Candamo M, Kanwal R, Shukla S, MacLennan GT, Gupta S. Role of class I histone deacetylases in the regulation of maspin expression in prostate cancer. Mol Carcinog. 2020 Aug;59(8):955-966. doi: 10.1002/mc.23214. Epub 2020 May 11. |
| 32653824 | Result | Xie Y, Tang P, Xing X, Zhao Y, Cao S, Liu S, Lu X, Zhong L. In situ exploring Chidamide, a histone deacetylase inhibitor, induces molecular changes of leukemic T-lymphocyte apoptosis using Raman spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc. 2020 Nov 5;241:118669. doi: 10.1016/j.saa.2020.118669. Epub 2020 Jul 2. |
| 20060381 | Result | Liu L, Chen B, Qin S, Li S, He X, Qiu S, Zhao W, Zhao H. A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells. Biochem Biophys Res Commun. 2010 Feb 5;392(2):190-5. doi: 10.1016/j.bbrc.2010.01.011. Epub 2010 Jan 7. |
| 33298132 | Result | Wang H, Liu YC, Zhu CY, Yan F, Wang MZ, Chen XS, Wang XK, Pang BX, Li YH, Liu DH, Gao CJ, Liu SJ, Dou LP. Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway. J Exp Clin Cancer Res. 2020 Dec 9;39(1):278. doi: 10.1186/s13046-020-01792-8. |
| 33637599 | Result | Que Y, Zhang XL, Liu ZX, Zhao JJ, Pan QZ, Wen XZ, Xiao W, Xu BS, Hong DC, Guo TH, Shen LJ, Fan WJ, Chen HY, Weng DS, Xu HR, Zhou PH, Zhang YZ, Niu XH, Zhang X. Frequent amplification of HDAC genes and efficacy of HDAC inhibitor chidamide and PD-1 blockade combination in soft tissue sarcoma. J Immunother Cancer. 2021 Feb;9(2):e001696. doi: 10.1136/jitc-2020-001696. |
| 34433253 | Result | Tu K, Yu Y, Wang Y, Yang T, Hu Q, Qin X, Tu J, Yang C, Kong L, Zhang Z. Combination of Chidamide-Mediated Epigenetic Modulation with Immunotherapy: Boosting Tumor Immunogenicity and Response to PD-1/PD-L1 Blockade. ACS Appl Mater Interfaces. 2021 Aug 25;13(33):39003-39017. doi: 10.1021/acsami.1c08290. Epub 2021 Aug 16. |
| 34539893 | Result | He Y, Jiang D, Zhang K, Zhu Y, Zhang J, Wu X, Xia J, Zhu Y, Zou L, Hu J, Cui Y, Zhou W, Chen F. Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy. J Cancer. 2021 Aug 27;12(20):6198-6208. doi: 10.7150/jca.61602. eCollection 2021. |
| 32792859 | Result | Ding N, You A, Tian W, Gu L, Deng D. Chidamide increases the sensitivity of Non-small Cell Lung Cancer to Crizotinib by decreasing c-MET mRNA methylation. Int J Biol Sci. 2020 Jul 19;16(14):2595-2611. doi: 10.7150/ijbs.45886. eCollection 2020. |
| 26774139 | Result | Liu L, Qiu S, Liu Y, Liu Z, Zheng Y, Su X, Chen B, Chen H. Chidamide and 5-flurouracil show a synergistic antitumor effect on human colon cancer xenografts in nude mice. Neoplasma. 2016;63(2):193-200. doi: 10.4149/203_150422N214. |
| ID | Term |
|---|---|
| D003110 | Colonic Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| C547816 | N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide |
| C000707970 | tislelizumab |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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