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GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma

Primary Purpose

Biliary Tract Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Combination of Gemcitabine, Oxaliplatin, Donafenib and Tislelizumab
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Biliary Tract Carcinoma focused on measuring Donafenib, Tislelizumab, Effects, Safety

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥18 years and ≤75 years; ECOG physical condition score: 0~1; Histologically or cytologically confirmed advanced biliary tract carcinoma (including gallbladder, intrahepatic and extrahepatic cholangiocarcinoma); Preoperative imaging assessment of the disease stage was III/IV; At least one measurable lesion (according to mRECIST criteria) Child-Pugh classification : A or B The main organs function well, and the examination indicators meet the following requirements: Routine blood tests: Hemoglobin ≥90 g/L (no blood transfusion within 14 days);Neutrophil count ≥1.5×10^9/L; Platelet count ≥80×10^9/L; Biochemical examination: Total bilirubin ≤2×ULN (upper normal value); ALT or AST ≤ 2.5×ULN; Endogenous creatinine clearance ≥ 50 mL /min (Cockcroft-Gault formula); thyroid function:Thyroid function is normal, thyroid stimulating hormone TSH is defined to be within the normal range. If baseline TSH is outside the normal range, T3 and T4 can be included if they are within the normal range; Myocardial enzyme profile:The myocardial enzyme profile was in the normal range (if simple laboratory abnormalities that were not clinically significant as determined by the investigators could also be included); Estimated survival time ≥ 3 months; Sign the informed consent voluntarily; Good compliance, and family members willing to cooperate with follow-up. Exclusion Criteria: Patients with other uncured malignant tumors; Pregnant or lactating women who are required to withdraw from the clinical trial if they become pregnant during the study period; Previous antitumor therapy for the disease in this study; Participated in clinical trials of other drugs within one month; Patients with a known history of other systemic serious diseases before screening; Obstructive jaundice (after active treatment such as biliary drainage or stent, the patients can be included in the group after the liver function returns to normal); Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number greater than the upper limit of normal in the clinical laboratory of the study center); Active HCV infected persons (HCV antibody positive with HCV RNA levels above the lower limit of detection); Allergic to any investigational drug or excipient; Long-term unhealed wounds or incomplete healing fractures; Previous organ transplantation history; Abnormal coagulation function; Screening for overactivity/venous thrombosis events in the previous year, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism; Having a history of abuse of psychotropic substances and being unable to quit or having mental disorders; A history of immune deficiency or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; Concomitant conditions that, in the investigator's judgment, seriously endanger the patient's safety or affect the patient's completion of the study.

Sites / Locations

  • Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

experimental group

Arm Description

Combination of Gemox, Donafenib and Tislelizumab

Outcomes

Primary Outcome Measures

Overall response rate
objective response rate(ORR),defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1
Conversion rate
Conversion rate, defined as the percentage of the conversion of patients with BTC assessed as unresectable into resectable through interventions, including the conversion of unresectable into resectable in the scientific sense such as insufficient future liver remnant(FLR), as well as the conversion of R1 and R2 to R0.

Secondary Outcome Measures

1-year Recurrence free survival
1-year Recurrence free survival
Progression-free survival
progression-free survival(PFS), defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator
Overall survival
overall survival(OS), defined as the time from enrollment to death due to any cause.
Incidence and degree of Adverse Events and Serious Adverse Events
Incidence, severity, and relationship to study drugs of all adverse events (AEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs).

Full Information

First Posted
December 12, 2022
Last Updated
December 25, 2022
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05668884
Brief Title
GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma
Official Title
Effects and Safety of GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma:a Prospective, Single-arm, Single-center Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 18, 2022 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
In this phase 2 study, the investigators aim to evaluate the effects and safety of combined therapy using oxaliplatin and gemcitabine chemotherapy, Donafenib and Tislelizumab for patients with advanced biliary tract carcinoma.
Detailed Description
Most advanced biliary tract carcinoma (BTC) patients are often accompanied by local or distant metastases and lose the opportunity for surgical resection. For patients with advanced BTC who have been in stages III and IV (AJCC/UICC, V2, 2018), the survival time is less than 4 months, and there is currently no standard treatment. The Gemox chemotherapy (oxaliplatin + gemcitabine) has been used in the treatment of advanced BTC, but the efficacy is still unsatisfactory. Donafenib is a small molecule multi-kinase inhibitor, the main targets including VEGFR1-3, PDGFRα, RET(ret proto-oncogene ), c-KIT(KIT proto-oncogene, receptor tyrosine kinase), Raf,FLT3,have anti-angiogenic effects, have been proven effective in hepatocellular carcinoma. In recent years, monoclonal antibodies against programmed cell death protein 1 (PD1) have shown remarkable therapeutic effects in the treatment of various solid tumors. Prior to this, the combined treatment of GEMOX combined with Donafenib and Tislelizumab was proved satisfying safety. Meanwhile,the phase-I trial showed good efficacy in conversion rate and 6-month overall survival rate. Due to the limitted small sample size of the phase I trial, the investigators aim to expand the sample size to further verify the effects and safety of combined therapy in the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Biliary Tract Carcinoma
Keywords
Donafenib, Tislelizumab, Effects, Safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
experimental group
Arm Type
Experimental
Arm Description
Combination of Gemox, Donafenib and Tislelizumab
Intervention Type
Combination Product
Intervention Name(s)
Combination of Gemcitabine, Oxaliplatin, Donafenib and Tislelizumab
Intervention Description
Combination of Gemcitabine, Oxaliplatin, Donafenib and Tislelizumab every 3 weeks
Primary Outcome Measure Information:
Title
Overall response rate
Description
objective response rate(ORR),defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1
Time Frame
6 months
Title
Conversion rate
Description
Conversion rate, defined as the percentage of the conversion of patients with BTC assessed as unresectable into resectable through interventions, including the conversion of unresectable into resectable in the scientific sense such as insufficient future liver remnant(FLR), as well as the conversion of R1 and R2 to R0.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
1-year Recurrence free survival
Description
1-year Recurrence free survival
Time Frame
1 year
Title
Progression-free survival
Description
progression-free survival(PFS), defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator
Time Frame
6 months
Title
Overall survival
Description
overall survival(OS), defined as the time from enrollment to death due to any cause.
Time Frame
6 months
Title
Incidence and degree of Adverse Events and Serious Adverse Events
Description
Incidence, severity, and relationship to study drugs of all adverse events (AEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs).
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years and ≤75 years; ECOG physical condition score: 0~1; Histologically or cytologically confirmed advanced biliary tract carcinoma (including gallbladder, intrahepatic and extrahepatic cholangiocarcinoma); Preoperative imaging assessment of the disease stage was III/IV; At least one measurable lesion (according to mRECIST criteria) Child-Pugh classification : A or B The main organs function well, and the examination indicators meet the following requirements: Routine blood tests: Hemoglobin ≥90 g/L (no blood transfusion within 14 days);Neutrophil count ≥1.5×10^9/L; Platelet count ≥80×10^9/L; Biochemical examination: Total bilirubin ≤2×ULN (upper normal value); ALT or AST ≤ 2.5×ULN; Endogenous creatinine clearance ≥ 50 mL /min (Cockcroft-Gault formula); thyroid function:Thyroid function is normal, thyroid stimulating hormone TSH is defined to be within the normal range. If baseline TSH is outside the normal range, T3 and T4 can be included if they are within the normal range; Myocardial enzyme profile:The myocardial enzyme profile was in the normal range (if simple laboratory abnormalities that were not clinically significant as determined by the investigators could also be included); Estimated survival time ≥ 3 months; Sign the informed consent voluntarily; Good compliance, and family members willing to cooperate with follow-up. Exclusion Criteria: Patients with other uncured malignant tumors; Pregnant or lactating women who are required to withdraw from the clinical trial if they become pregnant during the study period; Previous antitumor therapy for the disease in this study; Participated in clinical trials of other drugs within one month; Patients with a known history of other systemic serious diseases before screening; Obstructive jaundice (after active treatment such as biliary drainage or stent, the patients can be included in the group after the liver function returns to normal); Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number greater than the upper limit of normal in the clinical laboratory of the study center); Active HCV infected persons (HCV antibody positive with HCV RNA levels above the lower limit of detection); Allergic to any investigational drug or excipient; Long-term unhealed wounds or incomplete healing fractures; Previous organ transplantation history; Abnormal coagulation function; Screening for overactivity/venous thrombosis events in the previous year, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism; Having a history of abuse of psychotropic substances and being unable to quit or having mental disorders; A history of immune deficiency or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; Concomitant conditions that, in the investigator's judgment, seriously endanger the patient's safety or affect the patient's completion of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lu Wang, M.D.
Phone
86-18121299357
Email
w.lr@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yiming Zhao, M.D.
Phone
13917307629
Email
gomas1711@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yiming Zhao, M.D.
Organizational Affiliation
Fudan University
Official's Role
Study Director
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200062
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lu Wang, M.D.
Phone
+86-18121299357
Email
w.lr@hotmail.com
First Name & Middle Initial & Last Name & Degree
Yiming Zhao, M.D.

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma

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