HDAC Inhibitor Combination with Chemoimmunotherapy in the Neoadjuvant Treatment of PMMR Locally Advanced Colon Cancer

NCT06709885 | Recruiting Phase 2 DMC

• 1 other identifier: TRIUNITE-02
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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?

Conditions

Colon Adenocarcinoma

Keywords

HDAC inhibitors; pMMR/MSS; neoadjuvant immunochemotherapy; Oxaliplatin; Capecitabine

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• Disease-free survival

  3 years

• Overall survival (OS)

  3 years

• MPR

  From enrollment to 12 Weeks of treatment end

• Curative resection

  From enrollment to 12 Weeks of treatment end

• ORR

  From enrollment to 12 Weeks of treatment end

Study Arms (2)

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)

Drug: Chidamide + Tislelizumab + chemotherapy (CapeOX )

Neoadjuvant chemotherapy (CapeOX)

ACTIVE COMPARATOR

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

Drug: CapeOX

Interventions

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

Chidamide + Tislelizumab + chemotherapy (CapeOX )

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

Neoadjuvant chemotherapy (CapeOX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.;

You may not qualify if:

• 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);
• \. 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.
• \. 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;

Sponsors & Collaborators

• Daping Hospital and the Research Institute of Surgery of the Third Military Medical University: lead
• Southwest Hospital, China: collaborator
• Xinqiao Hospital of Chongqing: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator
• The Second Affiliated Hospital of Chongqing Medical University: collaborator
• Chongqing Medical University: collaborator
• Chongqing University Cancer Hospital: collaborator
• Chongqing General Hospital: collaborator
• Chongqing Traditional Chinese Medicine Hospital: collaborator
• Chongqing Shapingba District People's Hospital: collaborator
• Chongqing Seventh People's Hospital: collaborator
• Chongqing Renji Hospital, University of Chinese Academy of Sciences: collaborator
• The 13th People's Hospital of Chongqing: collaborator

Study Sites (1)

Daping Hospital， Third Military Medical University

Chongqing, Chongqing Municipality, 400000, China

RECRUITING

Related Publications (15)

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MeSH Terms

Conditions

Colonic Neoplasms

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; tislelizumab; Drug Therapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• fan Li, PhD

  Third Military Medical University

  STUDY CHAIR

Central Study Contacts

fan li, PhD

CONTACT

18696539200; levinecq@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2024
• First Posted: November 29, 2024
• Study Start: October 15, 2024
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2027
• Last Updated: November 29, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)