Clinical trial NCT05653817: Advanced or Metastatic Cholangiocarcinoma
Official title: A Multicenter Clinical Study of Carralizumab Combined With Albumin Paclitaxel and Apatinib Mesylate in the Second-line Treatment of Advanced or Metastatic Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cholangiocarcinoma
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2022-12-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open, multicenter trial of carralizumab in combination with albumin paclitaxel and apatinib mesylate for the second-line treatment of patients with advanced or metastatic cholangiocarcinoma. The study enlists patients with histopathologically or cytologically confirmed unresectable, recurrent, or metastatic cholangiocarcinoma (including intrahepatic, extrahepatic, and distal cholangiocarcinoma). Previously, she had received systematic internal medicine anti-tumor therapy with gemcitabine regimen as standard, which met the inclusion criteria of this study. She was given oral therapy with albumin binding paclitaxel combined with carrilizumab and apatinib mesylate. Treatment continued or was evaluated every 2 cycles until disease progression or toxic side effects of patient intolerance to the treatment regimen. To evaluate progression-free survival (PFS) in second-line therapy with carrilizumab in combination with albumin paclitaxel and apatinib mesylate in patients with advanced or metastatic cholangiocarcinoma.

Detailed description: Cholangiocarcinoma (CCA) is a cancer that easily invades adjacent structures. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) are increased in most types of cancer and inhibit tumor progression by blocking VEGF/VEGFR2 \[16\]. Apatinib is a highly selective VEGFR2 antagonist that inhibits apoptosis and growth of CCA cells. Apatinib is also a derivative of PTK787, and its targets include VEGFR-1, VEGFR-2, PDGFR, c-kit, c-Src, etc. The activity of Apatinib against VEGFR-2 is 137 times that of PTK787, the IC50 is only 1nmol/L, and it can strongly inhibit tumor angiogenesis. At the same time, it can also inhibit the downstream signal transduction mediated by KDR and inhibit tumor growth.

Eligibility criteria: Inclusion Criteria:

1. Patients with advanced, pathologically unresectable or metastatic bile duct epithelial cell carcinoma;
2. Previously received a chemotherapy regimen (including gemcitabine) anti-tumor systemic therapy, but did not use albumin binding paclitaxel;
3. Age ≥18 years old and under 75 years old;
4. Predicted survival ≥3 months;
5. ECOG score 0-1;
6. Child-Pugh score\<8
7. There was at least one measurable tumor lesion with a long diameter ≥10 mm and a short diameter ≥15 mm on spiral CT. For general CT or physical examination, the maximum diameter must be ≥20mm;
8. The results of liver and kidney function and blood routine examination within 1 week before enrollment were consistent with the following conditions， ANC≥1.5×10\^9/L,PLT≥80×10\^9/L,HGB≥80g/L,Cr≤1.5×ULN,TBIL≤2.5×ULN,ALP≤2.5×ULN,AST≤2.5×ULN,ALT≤2.5×ULN
9. Patients participate voluntarily and sign informed consent forms

Exclusion Criteria:

1. Known to be severely allergic to carrilizumab, apatinib, and albumin paclitaxel;
2. Obstructive jaundice cannot be achieved 2.5×ULN after surgical intervention;
3. Patients with biliary obstruction that may occur or worsen within 4 to 6 weeks;
4. Patients with obvious coagulation mechanism disorder, active bleeding and bleeding tendency;
5. History of other malignancies within 5 years (fully treated basal cell carcinoma of the skin, out-of-situ cervix);
6. Interstitial pneumonia or pulmonary fibrosis;
7. Uncontrollable pleural effusion or ascites;
8. Severe uncontrolled medical disease, acute infection, recent history of myocardial infarction (within 3 months);
9. Pregnant or lactating mothers who refused to use appropriate contraceptive methods during the course of this study;
10. The researchers determined that the patients were not suitable for this study.

Primary outcomes:
measure: PFS
timeFrame: 24month
Secondary outcomes:
measure: OS
timeFrame: 24month
Other outcomes:
Locations:
Study officials:
affiliation: First hospital of Xi'an Jiaotong University
name: enxiao li, PHD
role: PRINCIPAL_INVESTIGATOR
References: