Combining Fruquintinib, Chidamide, and Sintilimab for Advanced Colorectal Cancer Treatment

A Prospective Single-arm Phase Ib/II Study on the Safety and Efficacy of Fruquintinib Plus Chidamide and Sintilimab in the Third and Later Line Treatment of MSS/pMMR Metastatic Colorectal Cancer

This study is testing a new combination of three drugs to see if it can help people with advanced colorectal cancer that hasn't improved with other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: sintilimab, bevacizumab, fruquintinib, chemotherapy
• Locations: 1 site (Beijing)
• Trial ID: NCT06685276 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a combination treatment involving fruquintinib, chidamide, and sintilimab for patients with unresectable locally advanced or metastatic colorectal cancer that has not responded to standard therapies. The study focuses on patients with microsatellite stable or proficient mismatch repair colorectal cancer, building on previous findings from the CAPability-01 trial. Participants will receive these treatments to assess their effectiveness in improving patient outcomes in this challenging cancer setting.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with unresectable metastatic colorectal adenocarcinoma that has failed standard second-line treatment.

Not a fit: Patients with colorectal cancer that is resectable or those who have not failed second-line systemic treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced colorectal cancer who have limited treatment choices.

How similar studies have performed: Previous studies, such as the CAPability-01 trial, have shown promising results with similar treatment combinations, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Fully understand this study and voluntarily sign the informed consent form;
2. Age between 18-75 years inclusive;
3. Patients with histologically confirmed unresectable locally advanced, recurrent, or metastatic colorectal adenocarcinoma;
4. Failure of standard second-line systemic treatment with measurable lesions;
5. Tumor tissue tested for microsatellite stability (MSS) or low microsatellite instability (MSI-L) by PCR, or confirmed pMMR by immunohistochemistry for DNA mismatch repair (MMR) protein (including MLH1, MSH2, MSH6, and PMS2 protein expression);
6. ECOG performance status of 0-2, with no deterioration within 7 days;
7. BMI≥18;
8. Expected survival ≥3 months;
9. Major organ functions meet the following requirements (no use of any blood components and growth factors within 14 days before enrollment):

   * Absolute neutrophil count ≥1.5×109/L, white blood cells ≥4.0×109/L;
   * Platelets ≥100×109/L;
   * Hemoglobin ≥90g/L;
   * Total bilirubin TBIL ≤1.5 times ULN;
   * ALT and AST ≤5 times ULN;
   * Urea/BUN and creatinine (Cr) ≤1.5×ULN (and creatinine clearance (CCr) ≥ 50mL/min);
   * Left ventricular ejection fraction (LVEF) ≥50%;
   * Corrected QT interval by Fridericia's formula (QTcF) \<470 milliseconds.
   * INR ≤1.5×ULN, APTT ≤1.5×ULN.
10. Women of childbearing age must use effective contraception;
11. Good compliance and cooperation with follow-up.

Exclusion Criteria:

1. Unable to comply with the study protocol or procedures;
2. Pregnant or breastfeeding women;
3. Concurrent with any of the following conditions: uncontrolled hypertension, coronary artery disease, arrhythmias, and heart failure;
4. Previous treatment with small molecule tyrosine kinase inhibitors for metastatic disease;
5. Previous treatment with romidepsin;
6. Previous treatment with immune checkpoint inhibitors for metastatic disease;
7. Uncontrollable severe concurrent infections;
8. Acute myocardial infarction, acute coronary syndrome, or CABG within 3 months before the first treatment;
9. Subjects allergic to the study medication or any of its excipients;
10. Known human immunodeficiency virus (HIV) infection. Known clinically significant liver disease history, including viral hepatitis \[known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (\>1×10\^4 copies/mL or \>2000 IU/mL); known hepatitis C virus (HCV) infection and HCV RNA positive (\>1×10\^3 copies/mL)\];

12\. Patients whom the investigator deems inappropriate for inclusion in this study.

Where this trial is running

Beijing

• China PLAGH — Beijing, China (Recruiting)

Conditions Colorectal Cancer Metastatic