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Colon AdenocarcinomaPhase 2NCT06709885

HDAC Inhibitor Combination With Chemoimmunotherapy in the Neoadjuvant Treatment of pMMR Locally Advanced Colon Cancer

A Phase 2 study testing Chidamide + Tislelizumab + chemotherapy (CapeOX ) and CapeOX in people with Colon Adenocarcinoma, run by Daping Hospital and the Research Institute of Surgery of the Third Military Medical University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Adenocarcinoma
What is being tested?
Chidamide + Tislelizumab + chemotherapy (CapeOX ) and CapeOX
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteChina
Study dates
15 Oct 2024to 30 Sep 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent to voluntarily join this study
  • Patients with colon cancer who are assessed by abdominal contrast-enhanced CT/abdominopelvic MRI as high-risk T3 (tumor destroys muscle wall and extends to pericolonic fat, protruding more than 5 mm into adjacent mesenteric fat) or T4 (tumor penetrates the visceral peritoneal surface or directly invades or adheres to adjacent organs or structures).
  • Adenocarcinoma of the colon confirmed by histopathological examination.
  • At least 18 years old, male or female.
  • Uncomplicated primary tumors (Perforation ； obstruction and bleeding that cannot be relieved by intervention)
  • The lower edge of the tumor is more than 12cm away from the anus.
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate bone marrow, liver, renal, and coagulation function as assessed by the laboratory as required by the protocol
  • Have not received any anti-tumor therapy for cancer in the past, including radiotherapy, chemotherapy, surgery, etc.;

Who cannot join

  • 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:
  • Received any treatment against the mechanism of action of tumor immunity, such as immunization, HDACi, etc.
  • Immunosuppressive drugs, or systemic hormonal drugs within 2 weeks prior to the first use of the study drug to achieve immunosuppressive purposes
  • Receipt of a live attenuated vaccine within 4 weeks prior to the first use of study drug;
  • Major surgery or severe trauma within 4 weeks prior to the first use of study drug;
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  • Receipt of systemic non-specific immunomodulatory therapy within 2 weeks prior to the first dose; Have received Chinese herbal medicines or proprietary Chinese medicines with anti-tumor indications within 2 weeks before the first dose.
  • 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;

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

fan li, PhD contact

18696539200

levinecq@163.com

China1 site, 1 recruiting

  • Daping Hospital， Third Military Medical University

    Chongqing, Chongqing Municipality, 400000

    fan li, PhD, 18696539200, levinecq@163.com

    Recruiting

Other trials in China

About this study

Official title: HDAC Inhibitor Combination With Immunochemotherapy in the Neoadjuvant Treatment of pMMR Locally Advanced Colon Cancer: A Multicenter, Double-arm, Phase II Randomized Controlled Study

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?

Being tested
Chidamide + Tislelizumab + chemotherapy (CapeOX ), CapeOX
Keywords
HDAC inhibitors, pMMR/MSS, neoadjuvant immunochemotherapy, Oxaliplatin, Capecitabine
Medical subject headings
Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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) ；After completing the surgery, Post-operation 4 cycles of Capeox

  • CapeOXDrug

    4 cycles (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ） Post-operation 4 cycles of Capeox

Study groups in NCT06709885
Study groupRoleWhat they receive
Chidamide + Tislelizumab + chemotherapy (CapeOX )Experimental4 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)
Receives: Drug: Chidamide + Tislelizumab + chemotherapy (CapeOX )
Neoadjuvant chemotherapy (CapeOX)Active comparator4 cycles Capeex (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ）
Receives: Drug: CapeOX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. pCR

    pCR was defined as the absence, from surgical samples, of malignant cells in the primary site and regional lymph nodes

    Measured: The pCR rate will be evaluated after surgery, an average of 12 weeks

Secondary outcomes (8)

  1. Disease-free survival

    Defined as the time from randomization to relapse or death, whichever occurred first.

    Measured: 3 years

  2. 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

    Measured: 3 years

  3. 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

    Measured: From enrollment to 12 Weeks of treatment end

  4. Curative resection

    Curative resection defined as complete tumor resection with all margins being negative.

    Measured: From enrollment to 12 Weeks of treatment end

  5. ORR

    Objective response is defined as a complete response (CR) or response (PR) according to RECIST v1.1

    Measured: From enrollment to 12 Weeks of treatment end

  6. 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).

    Measured: From enrollment to 12 Weeks of treatment end

  7. Postoperative complications

    Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.

    Measured: 3 years

  8. Grade 3-4 adverse effects rate

    Rate of chemotherapy andHDACI and immunotherapy related severe adverse events

    Measured: From date of randomization until the date of death from any cause, assessed up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Nov 2024
  2. Study start15 Oct 2024
  3. Primary completion30 Sep 2025 (estimated)
  4. Study completion30 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06709885
Sponsor's protocol ID
TRIUNITE-02
Status last verified
Sep 2024
First submitted
13 Oct 2024
Last updated
29 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32702383

  • 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.

    PubMed 36657089

  • 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.

    PubMed 38564700

  • 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.

    PubMed 11171826

  • 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.

    PubMed 28596308

  • 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.

    PubMed 23432814

  • 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.

    PubMed 32391971

  • 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.

    PubMed 32653824

  • 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.

    PubMed 20060381

  • 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.

    PubMed 33298132

  • 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.

    PubMed 33637599

  • 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.

    PubMed 34433253

  • 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.

    PubMed 34539893

  • 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.

    PubMed 32792859

  • 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.

    PubMed 26774139

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Chidamide + Tislelizumab + chemotherapy (CapeOX ) and CapeOX in people with Colon Adenocarcinoma, run by Daping Hospital and the Research Institute of Surgery of the Third Military Medical University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact fan li, PhD (18696539200, levinecq@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

pCR (time frame: The pCR rate will be evaluated after surgery, an average of 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06709885, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.

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