Chidamide in Combination With PD-1 Inhibitor, Bevacizumab, and XELOX for Metastatic Colorectal Cancer

A Phase II Clinical Study of Chidamide in Combination With PD-1 Inhibitor, Bevacizumab, and XELOX as First-Line Treatment for Metastatic Colorectal Cancer

This phase II, open-label, dose-escalation study aims to (1) assess the safety and tolerability of chidamide in combination with PD-1 inhibitor, bevacizumab, and XELOX as first-line therapy for treatment-naïve metastatic colorectal cancer patients, (2) establish the recommended phase II dose (RP2D) of the combination regimen, and (3) obtain preliminary efficacy data including objective response rate (ORR) and progression-free survival (PFS).

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Treatment group; Drug: Standard-of-care control group

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years and ≤75 years, regardless of gender; Histologically confirmed unresectable metastatic/recurrent colorectal adenocarcinoma; No prior systemic antitumor therapy received for metastatic/recurrent colorectal adenocarcinoma; For subjects who have received prior neoadjuvant/adjuvant therapy, the interval between the last treatment and recurrence/progression must exceed 12 months; ECOG performance status 0-1; At least one measurable lesion (per RECIST v1.1 criteria); Expected survival ≥3 months;

Organ function must meet the following requirements prior to the first dose of the investigational drug:

1. Hematological function (no blood transfusion or growth factor administration within 14 days before screening):

   Absolute neutrophil count ≥1.5×10^9/L, Platelet count ≥100×10^9/L, Hemoglobin ≥90 g/L;

2. Hepatic and renal function (no albumin infusion within 14 days before screening):

   Total bilirubin ≤1.5×ULN, Serum albumin ≥25 g/L, ALT and AST ≤2.5×ULN (≤5.0×ULN for patients with liver metastases), Serum creatinine ≤1.5×ULN;

3. Coagulation function:

   INR ≤1.5×ULN, PT and APTT ≤1.5×ULN;

4. Urinalysis:

Urine protein <2+; for subjects with baseline urine protein ≥2+, 24-hour urine protein quantification must be <1 g; Subjects (including females and males) must agree to use effective contraception from signing the informed consent form until 180 days after the last dose of the investigational drug. Females of childbearing potential must not be pregnant or breastfeeding; Prior treatment-related adverse events (AEs) must have resolved to ≤Grade 1 (per NCI CTCAE v5.0, except alopecia); Voluntary participation in this clinical trial with written informed consent.

Exclusion Criteria:

• Subjects with known tumor microsatellite instability-high (MSI-H) status.

Prior treatment with histone deacetylase (HDAC) inhibitors, including but not limited to chidamide or entinostat.

Prior postoperative adjuvant therapy targeting EGFR or VEGF/VEGFR, including bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, or biosimilars of these agents.

Prior treatment with T-cell co-stimulation or immune checkpoint therapies, including CTLA-4 inhibitors, PD-1/PD-L1/PD-L2 inhibitors, or other T-cell-targeted drugs.

Active hepatitis B (HBV DNA ≥ 500 IU/mL) or hepatitis C (HCV antibody-positive with HCV-RNA above the lower limit of detection).

Central nervous system (CNS) metastases or leptomeningeal metastases.

History of cerebrovascular accident, myocardial infarction, unstable angina, or poorly controlled arrhythmia within the past 6 months (including QTc interval ≥ 450 ms in males or ≥ 470 ms in females, calculated via Fridericia's formula).

Clinically uncontrolled pleural effusion, ascites, or pericardial effusion requiring intervention and deemed ineligible by the investigator.

Cardiac dysfunction (NYHA class III/IV) or left ventricular ejection fraction (LVEF) < 50% on echocardiography.

History of other malignancies within 5 years prior to signing informed consent, except cured basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ.

Immunodeficiency, including HIV positivity, congenital/acquired immune deficiency, or history of organ/allogeneic bone marrow transplantation.

Active autoimmune disease or autoimmune disease history (e.g., interstitial pneumonia, colitis, hepatitis, thyroid dysfunction). Exceptions: vitiligo, childhood asthma/allergies in remission without adult intervention, stable hypothyroidism on hormone replacement, or type I diabetes on stable insulin.

Uncontrolled hypertension (systolic ≥ 150 mmHg and/or diastolic ≥ 100 mmHg).

History of hypertensive crisis or hypertensive encephalopathy.

Systemic corticosteroid use (>10 mg prednisone daily or equivalent) or immunosuppressants within 2 weeks prior to treatment.

Active systemic infection requiring IV antibiotics >7 days within 2 weeks prior to treatment.

Anti-tuberculosis therapy within 1 year prior to treatment.

History of substance abuse, alcoholism, or psychiatric/neurological disorders (e.g., epilepsy, dementia, hepatic encephalopathy).

Participation in other clinical trials with investigational drugs within 4 weeks prior to treatment.

Hypersensitivity to macromolecular protein preparations or any component of the study drugs.

Live vaccination within 4 weeks prior to treatment.

Major surgery within 4 weeks prior to treatment or planned during the study.

Hemoptysis (≥2.5 mL of bright red blood) or clinically significant gastrointestinal bleeding within 2 months prior to treatment.

Current or history of gastrointestinal obstruction, unless resolved with treatment and deemed eligible by the investigator.

Hemorrhagic tendency or clinically significant coagulopathy.

Unhealed wounds, active ulcers, or untreated fractures.

Recent use of antiplatelet/anticoagulant agents:

Aspirin (>325 mg/day) or clopidogrel (>75 mg/day) within 10 days prior to treatment;

Therapeutic anticoagulation (except low-molecular-weight heparin) within 2 weeks prior to treatment.

Gastrointestinal abnormalities affecting drug absorption (e.g., dysphagia, chronic diarrhea, gastrectomy).

Any condition that, in the investigator's judgment, increases study risk, confounds results, or renders the patient unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; PD-1 inhibitor: Dose determined per the manufacturer's instructions or investigator's discretion based on patient status. Bevacizumab: 7.5 mg/kg via intravenous infusion every 3 weeks (Q3W). XELOX regimen: Oxaliplatin: 130 mg/m² via intravenous infusion on Day 1; Capecitabine: 1000 mg/m² orally twice daily on Days 1-14; Repeated every 3 weeks for 6 cycles. Maintenance therapy after 6 cycles (experimental group): Chidamide: Administered at the maximum tolerated dose/recommended phase II dose (MTD/RP2D), orally twice weekly (on Days 1, 4, 8, 11, 15, and 18 of each cycle), 30 minutes after meals. PD-1 inhibitor, Bevacizumab, and Capecitabine: Continued at the same doses and schedules as during the initial treatment phase.	Drug: Treatment group; Chidamide+XELOX + Bevacizumab+PD-1
Active Comparator: Standard-of-care control group; XELOX + Bevacizumab: Doses identical to the experimental group (Oxaliplatin 130 mg/m², Capecitabine 1000 mg/m², Bevacizumab 7.5 mg/kg Q3W) for 6 cycles. Maintenance therapy after 6 cycles: Bevacizumab (7.5 mg/kg Q3W) and Capecitabine (1000 mg/m² orally twice daily on Days 1-14 of each cycle).	Drug: Standard-of-care control group; XELOX + Bevacizumab+PD-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Evaluated using RECIST 1.1 criteria	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Evaluated using RECIST 1.1 criteria	24 months
Overall Survival (OS)	Evaluated using RECIST 1.1 criteria	24 months
safety	Based on NCI-CTCAE 5.0 criteria.	24 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): April 9, 2025
• Primary Completion (Estimated): January 8, 2026
• Study Completion (Estimated): January 8, 2028

Study Registration Dates

• First Submitted: February 28, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CSIIT-Q100

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No