Tests chidamide in advanced colorectal cancer with high SULF1 levels after prior treatments

Trial details

Who runs it

Sir Run Run Shaw Hospital

Trial code

NCT07927075

Record updated

9 November 2026

Original description

Previous studies have shown that HDAC inhibitors can inhibit SULF1 expression in CAFs. Chidamide, an HDAC inhibitor widely used in clinical practice, has demonstrated good efficacy in advanced breast cancer. Our retrospective study found that the higher the proportion of breast cancer patients with high fibroblast SULF1 expression, the more effective chidamide treatment was. Currently, the third-line treatment for advanced colorectal cancer consists of oral regorafenib or fruquintinib, but their median progression-free survival is only 2.3 and 3.7 months, respectively, and they are associated with significant adverse reactions such as rash, hypertension, and hyperbilirubinemia. The incidence of colorectal cancer continues to increase globally and in Asia; despite advances in advanced treatment, there remains a high unmet medical need, particularly for patients with refractory metastatic colorectal cancer. Chidamide is currently mainly used to treat relapsed or refractory peripheral T-cell lymphoma. Previous clinical studies in China and abroad have found that it also has good efficacy against various malignant tumors, including esophageal cancer, gastric cancer, lung cancer, nasopharyngeal carcinoma, breast cancer, liver cancer, cervical cancer, and leukemia. In summary, the proposed study evaluating the efficacy of chidamide in advanced refractory colorectal cancer with high SULF1 expression has important therapeutic value and high feasibility, supported by solid preliminary data. The objective of this study is to conduct a prospective, single-arm study in subjects with SULF1-high advanced colorectal cancer who have received at least 2 prior lines of standard therapy, to observe the efficacy and safety of chidamide. We hope this study will further clarify whether chidamide, a SULF1 inhibitor, can improve disease response rates, prolong response duration and survival time, and provide patients with advanced disease an opportunity to regain effective treatment.Read full original descriptionShow less

Evaluating the Efficacy of Chidamide in Advanced Refractory Colorectal Cancer With High SULF1 Expression

Previous studies have shown that HDAC inhibitors can inhibit SULF1 expression in CAFs. Chidamide, an HDAC inhibitor widely used in clinical practice, has demonstrated good efficacy in advanced breast cancer. Our retrospective study found that the higher the proportion of breast cancer patients with high fibroblast SULF1 expression, the more effective chidamide treatment was. Currently, the third-line treatment for advanced colorectal cancer consists of oral regorafenib or fruquintinib, but their median progression-free survival is only 2.3 and 3.7 months, respectively, and they are associated with significant adverse reactions such as rash, hypertension, and hyperbilirubinemia. The incidence of colorectal cancer continues to increase globally and in Asia; despite advances in advanced treatment, there remains a high unmet medical need, particularly for patients with refractory metastatic colorectal cancer. Chidamide is currently mainly used to treat relapsed or refractory peripheral T-cell lymphoma. Previous clinical studies in China and abroad have found that it also has good efficacy against various malignant tumors, including esophageal cancer, gastric cancer, lung cancer, nasopharyngeal carcinoma, breast cancer, liver cancer, cervical cancer, and leukemia. In summary, the proposed study evaluating the efficacy of chidamide in advanced refractory colorectal cancer with high SULF1 expression has important therapeutic value and high feasibility, supported by solid preliminary data. The objective of this study is to conduct a prospective, single-arm study in subjects with SULF1-high advanced colorectal cancer who have received at least 2 prior lines of standard therapy, to observe the efficacy and safety of chidamide. We hope this study will further clarify whether chidamide, a SULF1 inhibitor, can improve disease response rates, prolong response duration and survival time, and provide patients with advanced disease an opportunity to regain effective treatment.

Inclusion: This study plans to enroll patients diagnosed with advanced colorectal cancer who are treated at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Age ≥18 years; Voluntarily participate in this study and sign the informed consent form; Confirmed histological evidence of colon or rectal adenocarcinoma; ECOG performance status score of 0-1; Tumor SULF1 high expression confirmed by immunohistochemistry; Distant metastasis or unresectable locally advanced colon or rectal adenocarcinoma confirmed by CT or MR evaluation, and according to RECIST v1.1 criteria, at least one measurable lesion confirmed by independent central imaging review, and after multidisciplinary discussion, it is considered that local treatment (surgery, intervention, radiotherapy, etc.) will not be performed currently or in the near future (within 2 months); Patients with metastatic colorectal cancer who have received at least two prior lines of standard regimen therapy, including fluorouracil, oxaliplatin, and irinotecan; The following laboratory test values obtained within 7 days before treatment on Day 1 of each treatment cycle, with adequate organ function:; Hemoglobin ≥90 g/L, neutrophil count ≥1.5×10⁹/L, platelet count ≥75×10⁹/L, serum total bilirubin ≤1.5× upper limit of normal (ULN), aspartate aminotransferase ≤2×ULN, alanine aminotransferase ≤3×ULN, serum creatinine ≤1.5×ULN; Willing and able to comply with the study protocol and visit schedule; Expected survival of at least 12 weeks.

Exclusion: 1）Patients with severe infection, obstruction, active bleeding, or perforation requiring emergency surgery or stent placement; 2）History of prior or concurrent other active malignancies (except malignancies that have been curatively treated with no recurrence for more than 5 years, or carcinoma in situ that can be cured with adequate treatment); 3）Major surgery such as laparotomy, thoracotomy, or laparoscopic organ resection, or severe trauma within the previous 2 weeks; 4）Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within 12 months before study enrollment; 5）Thrombotic or embolic events within the previous 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, or deep vein thrombosis; 6）New York Heart Association (NYHA) class II or higher congestive heart failure; 7）Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related disease, or active hepatitis B or hepatitis C; 8）Active inflammatory bowel disease or other colorectal diseases causing chronic diarrhea; 9）Any unresolved CTCAE grade 2 or higher toxicity caused by prior treatment (except anemia, alopecia, and skin pigmentation); 10）Known or suspected history of allergy to any relevant drug used in the study; 11）Patients scheduled to undergo local treatment (surgery, intervention, radiotherapy, etc.) in the near future (within 2 months); 12）Any medical condition that is unstable or may affect patient safety and study compliance; 13）Radiotherapy within <4 weeks before the first dose of study drug, or chemotherapy, biological therapy, endocrine therapy, or small-molecule targeted therapy before the first dose of study drug (enrollment allowed if washout ≥5 half-lives from the first dose of study drug); 14）Insufficient hematopoietic function or organ function (correction with blood products such as transfusion within ≤14 days before the first dose of study drug is not allowed); 15）Vulnerable populations, including individuals with mental illness, cognitive impairment, critically ill patients, minors, pregnant women, illiterate individuals, etc.

ClinicalTrials.gov NCT07927075