Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab in Unresectable Biliary Tract Cancer

Efficacy and Safety of the Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab in Initially Unresectable Biliary Tract Cancer

Study design: Prospective, single-arm, single-center phase II clinical study; Primary endpoint: Conversion rate; Secondary endpoints: Safety, disease control rate, disease-free survival, and overall survival; Main characteristics of enrolled patients: Patients with initially unresectable biliary tract cancer; Interventions: Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab; Sample size: 34 patients; Treatment until: 1. successfully conversed to resectable disease 2. progressed disease 3. intolerable toxicity 4. patient requests withdrawal; Research process: In this study, patients who met the inclusion criteria were evaluated at the end of every 3 weeks of treatment, up to surgical treatment or disease progression; Safety evaluation: Evaluate adverse reactions according to CTCAE 4.0; Follow up: 12 months after the last case was enrolled.

Study Overview

• Status: Active, not recruiting
• Conditions: Biliary Tract Carcinoma; Initially Unresectable
• Intervention / Treatment: Drug: Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 and ≤80 years;
2. ECOG 0~1;
3. Histologically or cytologically confirmed carcinoma of the bile duct or gallbladder;
4. Imaging assessment of disease stage III/IVA/any TN1M0*;
5. The main organs have good functions and the examination indexes meet the following requirements:

6. Blood routine test:

   Hemoglobin ≥90 g/L (no blood transfusion within 14 days); Neutrophils count ≥1.5×10^9/L; Platelet count ≥80×10^9/L;

7. Biochemical tests:

   Total bilirubin ≤2×ULN (upper limit of normal value); Blood alanine aminotransferase (ALT) or blood aspartate aminotransferase (AST) ≤ 2.5×ULN; Endogenous creatinine clearance rate ≥ 50 mL /min (Cockcroft-Gault formula);

8. Voluntarily signed the informed consent;
9. Good compliance and family members are willing to cooperate with follow-up.

Exclusion Criteria:

1. Other uncured malignancies;
2. Pregnant or lactating women, if the subject becomes pregnant during the study period, should withdraw from the clinical trial;
3. Previous anti-tumor therapy for the disease in this study;
4. Participated in other drug clinical trials within one month;
5. Patients with known history of other systemic serious diseases before screening;
6. Long-term unhealed wounds or incomplete healed fractures;
7. Have a history of organ transplantation;
8. Abnormal blood coagulation, with bleeding tendency (14 days before randomization must meet: INR within the normal range without the use of anticoagulants); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogs; The use of low-dose warfarin (1 mg orally, once daily) or low-dose aspirin (not more than 100 mg daily) for prophylactic purposes is permitted, provided that INR is less than 1.5;
9. The incidence of arterial/venous thrombosis events in the previous year, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis and pulmonary embolism, was screened;
10. People with a history of psychotropic substance abuse and unable to get rid of it or with mental disorders; Have a history of immunodeficiency, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation;

12. Concomitant diseases that, in the Investigator's judgment, seriously endanger patient safety or affect patient completion of the 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: combined treatment group; Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab Gemcitabine: 1000mg/m^2, iv, d1, d8, q3w Oxaliplatin: 100mg/m^2, iv, d1, q3w Sintilimab: 200mg, iv, d1, q3w Bevacizumab: 5mg/kg, d1, q3w	Drug: Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab; Combination of Gemcitabine, Oxaliplatin, Sintilimab and Bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	objective response rate	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety：the incidence of adverse events and serious adverse events	Incidence of adverse events and serious adverse events	3 weeks
disease control rate	disease control rate	3 weeks
progress-free survival	progress-free survival	3 weeks
overall survival	overall survival	3 weeks

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gemcitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: 2020-176-2096

Drug and device information, study documents

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