Using HDAC inhibitors with chemoimmunotherapy for advanced colon cancer treatment

HDAC Inhibitor Combination With Immunochemotherapy in the Neoadjuvant Treatment of pMMR Locally Advanced Colon Cancer: A Multicenter, Double-arm, Phase II Randomized Controlled Study

This study is testing if adding HDAC inhibitors to chemotherapy and immunotherapy can help people with advanced colon cancer have better treatment results and improve their chances of recovery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Chongqing, Chongqing Municipality)
• Trial ID: NCT06709885 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and effectiveness of combining HDAC inhibitors with neoadjuvant immunochemotherapy in patients with locally advanced colon cancer. The study aims to determine if this combination can improve the rate of pathological complete response (pCR) and complete tumor resection compared to standard neoadjuvant therapy. It also seeks to evaluate the long-term prognosis and safety of this treatment approach. Participants will receive Chidamide and Tislelizumab alongside chemotherapy regimens like CapeOX.

Who should consider this trial

Good fit: Ideal candidates include adults with high-risk T3 or T4 locally advanced colon adenocarcinoma who have not received prior anti-tumor therapy.

Not a fit: Patients with complicated primary tumors or those who have received previous anti-tumor therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could enhance the effectiveness of current therapies for patients with advanced colon cancer, potentially leading to better outcomes.

How similar studies have performed: While the combination of HDAC inhibitors with immunochemotherapy is a novel approach, similar studies have shown promising results in other cancer types, suggesting potential for success.

Eligibility criteria

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;

Where this trial is running

Chongqing, Chongqing Municipality

• Daping Hospital， Third Military Medical University — Chongqing, Chongqing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: fan li, PhD

Conditions: Colon Adenocarcinoma, HDAC inhibitors, pMMR/MSS, neoadjuvant immunochemotherapy, Oxaliplatin, Capecitabine