drugset / Trial / NCT06709885
HDAC Inhibitor Combination With Chemoimmunotherapy in the Neoadjuvant Treatment of pMMR Locally Advanced Colon Cancer
Phase 2
Recruiting
100 enrolled
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Chongqing General Hospital · collabChongqing Medical University · collabChongqing Renji Hospital, University of Chinese Academy of Sciences · collabChongqing Seventh People's Hospital · collabChongqing Shapingba District People's Hospital · collabChongqing Traditional Chinese Medicine Hospital · collabChongqing University Cancer Hospital · collabFirst Affiliated Hospital of Chongqing Medical University · collabSouthwest Hospital, China · collabThe 13th People's Hospital of Chongqing · collabThe Second Affiliated Hospital of Chongqing Medical University · collabXinqiao Hospital of Chongqing · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
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?
Timeline
- Start
- 2024-10-15
- Primary completion
- 2025-09-30
- Completion
- 2027-09-30
Publications
- Results 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: [email protected]. 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
- Results 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Tislelizumab | Monoclonal antibody | 200 mg/m2 | Intravenous |
| Subject | Tucidinostat | Small molecule | 20 mg | Oral |
| Background | Capecitabine | Small molecule | 850 mg/m2 | Oral |
| Background | Capecitabine | Small molecule | 1000 mg/m2 | Oral |
| Background | Oxaliplatin | Small molecule | 130 mg/m2 | Intravenous |