Colorectal Cancer Metastatic
Conditions
Brief summary
The prognosis of most patients with unresectable locally advanced or metastatic colorectal cancer (CRC) remains poor despite the advancements in chemotherapy and target therapy. CAPability-01 trial investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Based on the previous findings of CAPability-01, we will further evaluate the efficacy and safety of sintilimab and chidamide in combination with fruquintinib in the same setting.
Interventions
DRUGFruquintinib
Fruquintinib: 5mg qd, po, 2 weeks on/1 week off, q3w, or 3mg qd, po, q3w.
DRUGSintilimab
Sintilimab: 200mg, iv, d1, q3w.
DRUGChidamide
Chidamide: 30mg/m2, po, biw.
Sponsors
Dai, Guanghai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progress-free Survival(PFS) | 24 months | The time from enrollment until tumor progression or death from any cause, whichever occurred first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 24 months | The proportion of patients with a PR or CR |
| Overall Survival (OS) | 24 months | The time calculated from enrollment until death from any cause, with living patients censored at the last known survival date |
| Disease control rate (DCR) | 24 months | The proportion of patients with a PR, CR, or SD |
| Duration of response (DoR) | 24 months | For patients who achieved a complete response (CR) or partial response (PR), the time from the first tumor assessment demonstrating response until disease progression or death, whichever occurred first |
Countries
China
Outcome results
None listed