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

November 25, 2024 updated by: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

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?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Chongqing
      • Chongqing, Chongqing, China, 400000
        • Recruiting
        • Daping Hospital, Third Military Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signed written informed consent to voluntarily join this study
  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:

  1. History of previous allergy to monoclonal antibodies, any component of HDACi, and capecitabine;

  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;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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)
Drug: 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
Active Comparator: Neoadjuvant chemotherapy (CapeOX)
4 cycles Capeex (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ）
Drug: CapeOX
4 cycles (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ） Post-operation 4 cycles of Capeox

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
The pCR rate will be evaluated after surgery, an average of 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival
Time Frame: 3 years
Defined as the time from randomization to relapse or death, whichever occurred first.
3 years
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 years
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
From enrollment to 12 Weeks of treatment end
Curative resection
Time Frame: From enrollment to 12 Weeks of treatment end
Curative resection defined as complete tumor resection with all margins being negative.
From enrollment to 12 Weeks of treatment end
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
From enrollment to 12 Weeks of treatment end
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).
From enrollment to 12 Weeks of treatment end
Postoperative complications
Time Frame: 3 years
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
3 years
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
From date of randomization until the date of death from any cause, assessed up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

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

Investigators

  • Study Chair: fan Li, PhD, Third Military Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 15, 2024

Primary Completion (Estimated)

September 30, 2025

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

October 13, 2024

First Submitted That Met QC Criteria

November 25, 2024

First Posted (Actual)

November 29, 2024

Study Record Updates

Last Update Posted (Actual)

November 29, 2024

Last Update Submitted That Met QC Criteria

November 25, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRIUNITE-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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