Clinical trial NCT06709885: HDAC Inhibitor Combination with Chemoimmunotherapy in the Neoadjuvant Treatment of PMMR Locally Advanced Colon Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colon Adenocarcinoma
Keywords: HDAC inhibitors
pMMR/MSS
neoadjuvant immunochemotherapy
Oxaliplatin
Capecitabine
Lead sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Sponsor class: OTHER
Collaborators: name: Southwest Hospital, China
name: Xinqiao Hospital of Chongqing
name: First Affiliated Hospital of Chongqing Medical University
name: The Second Affiliated Hospital of Chongqing Medical University
name: Chongqing Medical University
name: Chongqing University Cancer Hospital
name: Chongqing General Hospital
name: Chongqing Traditional Chinese Medicine Hospital
name: Chongqing Shapingba District People's Hospital
name: Chongqing Seventh People's Hospital
name: Chongqing Fifth Hospital RENJI Hospital Chongqing
name: The 13th People's Hospital of Chongqing
First posted: 2024-11-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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?


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 \&gt; 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;

Primary outcomes:
measure: pCR
timeFrame: The pCR rate will be evaluated after surgery, an average of 12 weeks
Secondary outcomes:
measure: Disease-free survival
timeFrame: 3 years
measure: Overall survival (OS)
timeFrame: 3 years
measure: MPR
timeFrame: From enrollment to 12 Weeks of treatment end
measure: Curative resection
timeFrame: From enrollment to 12 Weeks of treatment end
measure: ORR
timeFrame: From enrollment to 12 Weeks of treatment end
measure: Down-staging of primary tumors
timeFrame: From enrollment to 12 Weeks of treatment end
measure: Postoperative complications
timeFrame: 3 years
measure: Grade 3-4 adverse effects rate
timeFrame: From date of randomization until the date of death from any cause, assessed up to 3 years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Daping Hospital， Third Military Medical University
state: Chongqing
Study officials:
affiliation: Third Military Medical University
name: fan Li, PhD
role: STUDY_CHAIR
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