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

Phase 2

Recruiting

• Conditions: Colon Adenocarcinoma
• Interventions: Drug: Chidamide + Tislelizumab + chemotherapy (CapeOX ); Drug: CapeOX

• Registration Number: NCT06709885
• Lead Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

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?

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-10-13
• Study Start: 2024-10-15
• Study First Submitted QC: 2024-11-25
• Last Update Submitted: 2024-11-25
• Study First Posted: 2024-11-28
• Last Update Posted: 2024-11-28
• Primary Completion: 2025-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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);

8. 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.

9. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chidamide + Tislelizumab + chemotherapy (CapeOX )	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)
Neoadjuvant chemotherapy (CapeOX)	CapeOX	4 cycles Capeex (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ）

Primary Outcome Measures

Name	Time	Method
pCR	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 Outcome Measures

Name	Time	Method
Disease-free survival	3 years	Defined as the time from randomization to relapse or death, whichever occurred first.
Overall survival (OS)	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
MPR	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
Curative resection	From enrollment to 12 Weeks of treatment end	Curative resection defined as complete tumor resection with all margins being negative.
ORR	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
Down-staging of primary tumors	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).
Postoperative complications	3 years	Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Grade 3-4 adverse effects rate	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

Trial Locations

Locations (1)

Daping Hospital， Third Military Medical University; 🇨🇳 Chongqing, Chongqing, China