HDAC Inhibitor Combination with Chemoimmunotherapy in the Neoadjuvant Treatment of PMMR Locally Advanced Colon Cancer
NCT ID: NCT06709885
Last Updated: 2024-11-29
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
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RECRUITING
PHASE2
100 participants
INTERVENTIONAL
2024-10-15
2027-09-30
Brief Summary
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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?
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Chidamide + Tislelizumab + chemotherapy (CapeOX )
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)
Chidamide + Tislelizumab + chemotherapy (CapeOX )
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
Neoadjuvant chemotherapy (CapeOX)
4 cycles Capeex (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ）
CapeOX
4 cycles (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ） Post-operation 4 cycles of Capeox
Interventions
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Chidamide + Tislelizumab + chemotherapy (CapeOX )
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
CapeOX
4 cycles (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ） Post-operation 4 cycles of Capeox
Eligibility Criteria
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Inclusion Criteria
2. 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).
3. Adenocarcinoma of the colon confirmed by histopathological examination.
4. At least 18 years old, male or female.
5. Uncomplicated primary tumors (Perforation ； obstruction and bleeding that cannot be relieved by intervention)
6. The lower edge of the tumor is more than 12cm away from the anus.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Adequate bone marrow, liver, renal, and coagulation function as assessed by the laboratory as required by the protocol
9. Have not received any anti-tumor therapy for cancer in the past, including radiotherapy, chemotherapy, surgery, etc.;
Exclusion Criteria
2. Has received or is receiving any of the following treatments in the past:
1. Received any treatment against the mechanism of action of tumor immunity, such as immunization, HDACi, etc.
2. Immunosuppressive drugs, or systemic hormonal drugs within 2 weeks prior to the first use of the study drug to achieve immunosuppressive purposes
3. Receipt of a live attenuated vaccine within 4 weeks prior to the first use of study drug;
4. Major surgery or severe trauma within 4 weeks prior to the first use of study drug;
5. 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.
3. Has any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
4. dMMR/MSI-H;
5. Presence of cardiac clinical symptoms or diseases that are not well controlled,
6. 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,
7. 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;
18 Years
ALL
No
Sponsors
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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
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
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
OTHER
Responsible Party
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Principal Investigators
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fan Li, PhD
Role: STUDY_CHAIR
Third Military Medical University
Locations
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Daping Hospital， Third Military Medical University
Chongqing, Chongqing Municipality, China
Countries
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Central Contacts
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Facility Contacts
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fan li, PhD
Role: primary
References
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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.
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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.
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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.
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Other Identifiers
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TRIUNITE-02
Identifier Type: -
Identifier Source: org_study_id