Advanced or Metastatic Cholangiocarcinoma

A Multicenter Clinical Study of Carralizumab Combined With Albumin Paclitaxel and Apatinib Mesylate in the Second-line Treatment of Advanced or Metastatic Cholangiocarcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Drug: Carrilizumab; Drug: Albumin-bound paclitaxel; Drug: Apatinib

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: yangwei fan, phd; Phone Number: +8615029078171; Email: 1289271841@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Advanced or metastatic cholangiocarcinoma; A multicenter clinical study of carralizumab combined with albumin paclitaxel and apatinib mesylate in the second-line treatment of advanced or metastatic cholangiocarcinoma.Albumin-bound paclitaxel 125 mg/m2 d1,8; Carrilizumab 200mg Q3W d1; Apatinib mesylate tablet treatment: 250mg orally, once a day, continuous administration. Treatment continued or was evaluated every 2 cycles until disease progression or toxic side effects of patient intolerance to the treatment regimen.

Drug: Carrilizumab; Carrilizumab 200mg Q3W d1; Drug: Albumin-bound paclitaxel; Albumin-bound paclitaxel 125 mg/m2 d1,8; Drug: Apatinib; Apatinib mesylate tablets for treatment: 250mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free survival	24month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	24month

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Investigators: Principal Investigator: enxiao li, PHD, First hospital of Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 31, 2023
• Primary Completion (Anticipated): January 31, 2025
• Study Completion (Anticipated): January 31, 2026

Study Registration Dates

• First Submitted: December 9, 2022
• First Submitted That Met QC Criteria: December 9, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Albumin-Bound Paclitaxel; Apatinib
• Other Study ID Numbers: XJTU1AF2021LSK-062

Drug and device information, study documents

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