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

Официальное название

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

Обзор

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?

Вмешательства

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

Первичные конечные точки

• pCR [Срок оценки: The pCR rate will be evaluated after surgery, an average of 12 weeks]

Вторичные конечные точки (8)

• Disease-free survival [Срок оценки: 3 years]
• Overall survival (OS) [Срок оценки: 3 years]
• MPR [Срок оценки: From enrollment to 12 Weeks of treatment end]
• Curative resection [Срок оценки: From enrollment to 12 Weeks of treatment end]
• ORR [Срок оценки: From enrollment to 12 Weeks of treatment end]
• Down-staging of primary tumors [Срок оценки: From enrollment to 12 Weeks of treatment end]
• Postoperative complications [Срок оценки: 3 years]
• Grade 3-4 adverse effects rate [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 3 years]

Критерии участия

Критерии включения

• 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.
• 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.;

Критерии исключения

• 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;
• 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;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Daping Hospital， Third Military Medical University — Чунцин

Публикации

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• 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. PMID 36657089
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• 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. PMID 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. PMID 32653824

Идентификаторы

NCT: NCT06709885 · TRIUNITE-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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