Colon Adenocarcinoma
Conditions
Keywords
HDAC inhibitors, pMMR/MSS, neoadjuvant immunochemotherapy, Oxaliplatin, Capecitabine
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?
Interventions
DRUGChidamide + 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
DRUGCapeOX
4 cycles (q3w; Day1 Oxaliplatin, 130mg/m2, iv.gtt; Day1-Day14, capecitabine, 850-1000mg/m2, BID, PO. ） Post-operation 4 cycles of Capeox
Sponsors
Southwest Hospital, China
Xinqiao Hospital of Chongqing
First Affiliated Hospital of Chongqing Medical University
The Second Affiliated Hospital of Chongqing Medical University
Chongqing Medical University
Chongqing University Cancer Hospital
Chongqing General Hospital
Chongqing Traditional Chinese Medicine Hospital
Chongqing Shapingba District People's Hospital
Chongqing Seventh People's Hospital
Chongqing Renji Hospital, University of Chinese Academy of Sciences
The 13th People's Hospital of Chongqing
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Disease-free survival | 3 years | Defined as the time from randomization to relapse or death, whichever occurred first. |
| 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 |
| 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 |
Countries
China
Contacts
Primary Contactfan li, PhD
Outcome results
None listed