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NCT Number: NCT06709885

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

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?

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Daping Hospital, Third Military Medical University

Chongqing, Chongqing Municipality, 400000, China

Location status: Recruiting

Location contact

fan li, PhD

CONTACT

[email protected]

18696539200

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.;

Exclusion criteria

  • 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;

Treatment and study plan

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

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

Primary outcomes

  1. pCR

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

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

Secondary outcomes

  1. Disease-free survival

    Time frame: 3 years

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

  2. Overall survival (OS)

    Time frame: 3 years

    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

  3. MPR

    Time frame: From enrollment to 12 Weeks of treatment end

    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

  4. Curative resection

    Time frame: From enrollment to 12 Weeks of treatment end

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

  5. ORR

    Time frame: From enrollment to 12 Weeks of treatment end

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

  6. Down-staging of primary tumors

    Time frame: From enrollment to 12 Weeks of treatment end

    Down-staging of the resected tumour as measured by histopathological tumour diameter and stage according to the TNM staging system of AJCC (7th version).

  7. Postoperative complications

    Time frame: 3 years

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

  8. Grade 3-4 adverse effects rate

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

    Rate of chemotherapy andHDACI and immunotherapy related severe adverse events

Study contacts

Contact information is provided by the study sponsor or research team.

fan li, PhD

CONTACT

[email protected]

18696539200

Sponsors and collaborators

Lead sponsor

Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Other

Collaborators

  • Chongqing General Hospital
  • Chongqing Medical University
  • Chongqing Renji Hospital, University of Chinese Academy of Sciences
  • Chongqing Seventh People's Hospital
  • Chongqing Shapingba District People's Hospital
  • Chongqing Traditional Chinese Medicine Hospital
  • Chongqing University Cancer Hospital
  • First Affiliated Hospital of Chongqing Medical University
  • Southwest Hospital, China
  • The 13th People's Hospital of Chongqing
  • The Second Affiliated Hospital of Chongqing Medical University
  • Xinqiao Hospital of Chongqing

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2025
Study completion
2027
First posted
Nov 29, 2024
Registry last updated
Nov 29, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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