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Combination of Anti-PD-1 Antibody and Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma

Primary Purpose

Intrahepatic Cholangiocarcinoma by AJCC V8 Stage

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Combination therapy

Mono-chemotherapy

About this trial

This is an interventional treatment trial for Intrahepatic Cholangiocarcinoma by AJCC V8 Stage focused on measuring Intrahepatic Cholangiocarcinoma, Immunotherapy, anti-programmed-death-1 antibody

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma)
Has at least one measurable, evaluable lesions based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the research center investigator
Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet study criteria
Is willing to provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion
Has a life expectancy of greater than 3 months
Has adequate organ function
Has EOCG score 0 or 1
Has willing to voluntarily participate in clinical trial and sign informed consent

Exclusion Criteria:

Histology includes fibrolamellar, hepatocytes, sarcomatoid liver cancer, hepatocytes, hepatocellular carcinoma and other components. Or has had previous biliary tract cancer (intra-or extra hepatic cholangiocarcinoma) or combined with other cancer with an exception of basal cell carcinoma and squamous cell carcinoma of the skin carcinoma in situ that has been radical treated.
Has active tuberculosis and were receiving anti-tb treatment, or receiving anti-tb treatment within a year before were randomly assigned.
Has symptomatic or poorly controlled circulatory disease, such as Congestive heart failure(NYHA III-IV), arrhythmia instability, type I angina, coronary heart disease, etc
Has esophageal and gastric varices bleeding due to portal hypertension, or with history of inflammatory bowel disease, gastrointestinal perforation and intestinal obstruction, abdominal abscess, or chronic diarrhea.
Has life-threatening bleeding or venous thromboembolism events occurred in the first six months before enrollment, or the patient was prone to severe bleeding or coagulation dysfunction, or was undergoing thrombolytic therapy
Has active autoimmune disease requiring systemic treatment within the two years before enrollment , especially those with immunosuppressive drugs, who were unable to control or who needed large amounts of immunosuppressive drugs to control the disease, excluding topical glucose-corticosteroids or systemic use, and prednisone less than 10 milligrams per day
Has central nervous system disease with symptoms, such as primary brain tumor, stroke, epilepsy, etc. Patients who have undergone central nervous system or known brain metastases
Has acute or severe hepatitis infection, or a severe bacterial or bacterial infection in an active or clinically poorly controlled, or with congenital or acquired immune deficiency such human immunodeficiency virus (HIV) infected
Has previous allogeneic stem cell or parenchymal organ transplantation, including after liver transplantation
Has history of allergies to drugs involved in this study
Women who are pregnant or lactating, or who do not want to use contraception during the trial.

Sites / Locations

the First Affiliated Hospital, School of Medicine, Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Triprilumab in combination with chemotherapy of GP

Mono-chemotherapy of GP

Arm Description

Triprilumab, 240 mg, every 3 weeks (Q3W), Day 1 of each 3 week cycle PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity .

Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)

Time from first randomization to the first documented disease progression or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Overall Survival (OS)

Overall survival is defined as the time from randomization to death due to any cause.

Objective Response Rate (ORR) per RECIST 1.1

ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) as assessed by RECIST 1.1

Disease Control Rate(DCR)

DCR is defined as the percentage of participants who have a confirmed Complete Response or Partial Response as assessed by RECIST 1.1

Myopathologic response(MPR)

DCR is defined as the proportion of patients with residual survival tumor ≤10%, the evaluation requires two liver cancer pathologists to evaluate and judge. If the difference between the two pathologists' evaluation is ≤10%, the average value is taken as the pathological remission rate. If the difference is greater than 10%, a third pathologist is required to evaluate, and then the average of the two with a difference of less than 10% will be taken

Conversion surgical resection(R0) rate

the ratio of patients successfully converted into radical surgical resection by the treatment plan, in which the margin of the liver is negative

Adverse Events (AE)

Safety evaluation was done continuously during treatment by using CTCAE 5.0

Full Information

NCT ID

NCT04413734

First Posted

May 30, 2020

Last Updated

May 30, 2020

Sponsor

Zhejiang University

1. Study Identification

Unique Protocol Identification Number

NCT04413734

Brief Title

Combination of Anti-PD-1 Antibody and Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma

Official Title

Combination of Anti-PD-1 Antibody and Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Exploratory Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Recruiting

Study Start Date

April 22, 2020 (Actual)

Primary Completion Date

April 22, 2022 (Anticipated)

Study Completion Date

April 22, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This study is designed to observe and evaluate the safety and the efficacy of the anti-programmed-death-1 antibody (anti-PD-1) Triprilumab in combination with chemotherapy of Gemcitabine PLUS Cisplatin in patients who were advanced intrahepatic cholangiocarcinoma with no chance for primary surgery.

Detailed Description

Intrahepatic cholangiocarcinoma, also known as intrahepatic cholangiocarcinoma, is derived from intrahepatic bile duct epithelial cells, the second most common primary liver malignant tumor in china. but most (60% -70%) patients is diagnosed at the advanced stage . Gemcitabine plus cisplatin is the standard first-line advanced treatment recommended in international and domestic guidelines, but the treatment effect remains to be improved. The clinical benefits of immune therapies for HCC are emerging. Early clinical data already show the safety of immune checkpoint inhibition. This study is to analyze the safety and efficacy of immunotherapy Triprilumab Injection combined with Gemcitabine Injection plus Cisplatin Injection in patients with advanced intrahepatic cholangiocarcinoma. Patients who were aged 18 to 80 years with a histological or cytological diagnosis of intrahepatic cholangiocarcinoma，locally advanced or multiple liver metastases, including postoperative occurrence, will be enrolled in this trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Intrahepatic Cholangiocarcinoma by AJCC V8 Stage

Keywords

Intrahepatic Cholangiocarcinoma, Immunotherapy, anti-programmed-death-1 antibody

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Triprilumab in combination with chemotherapy of GP

Arm Type

Experimental

Arm Description

Arm Title

Mono-chemotherapy of GP

Arm Type

Active Comparator

Arm Description

Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity.

Intervention Type

Drug

Intervention Name(s)

Combination therapy

Other Intervention Name(s)

Triprilumab, Immunotherapy, Anti-PD-1 therapy

Intervention Description

Triprilumab by intravenous infusion accompanying with Gemcitabine plus Cisplatin

Intervention Type

Drug

Intervention Name(s)

Mono-chemotherapy

Other Intervention Name(s)

Gemcitabine Injection plus Cisplatin Injection

Intervention Description

Gemcitabine plus Cisplatin by intravenous infusion

Primary Outcome Measure Information:

Title

Progression-Free Survival (PFS)

Description

Time from first randomization to the first documented disease progression or death due to any cause, whichever occurs first.

Time Frame

Observation period 48 months

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

Overall survival is defined as the time from randomization to death due to any cause.

Time Frame

Up to 48 months

Title

Objective Response Rate (ORR) per RECIST 1.1

Description

Time Frame

Up to 48 months

Title

Disease Control Rate(DCR)

Description

DCR is defined as the percentage of participants who have a confirmed Complete Response or Partial Response as assessed by RECIST 1.1

Time Frame

Up to 48 months

Title

Myopathologic response(MPR)

Description

Time Frame

Up to 48 months

Title

Conversion surgical resection(R0) rate

Description

the ratio of patients successfully converted into radical surgical resection by the treatment plan, in which the margin of the liver is negative

Time Frame

Up to 48 months

Title

Adverse Events (AE)

Description

Safety evaluation was done continuously during treatment by using CTCAE 5.0

Time Frame

Up to 48 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma) Has at least one measurable, evaluable lesions based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the research center investigator Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet study criteria Is willing to provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion Has a life expectancy of greater than 3 months Has adequate organ function Has EOCG score 0 or 1 Has willing to voluntarily participate in clinical trial and sign informed consent Exclusion Criteria: Histology includes fibrolamellar, hepatocytes, sarcomatoid liver cancer, hepatocytes, hepatocellular carcinoma and other components. Or has had previous biliary tract cancer (intra-or extra hepatic cholangiocarcinoma) or combined with other cancer with an exception of basal cell carcinoma and squamous cell carcinoma of the skin carcinoma in situ that has been radical treated. Has active tuberculosis and were receiving anti-tb treatment, or receiving anti-tb treatment within a year before were randomly assigned. Has symptomatic or poorly controlled circulatory disease, such as Congestive heart failure(NYHA III-IV), arrhythmia instability, type I angina, coronary heart disease, etc Has esophageal and gastric varices bleeding due to portal hypertension, or with history of inflammatory bowel disease, gastrointestinal perforation and intestinal obstruction, abdominal abscess, or chronic diarrhea. Has life-threatening bleeding or venous thromboembolism events occurred in the first six months before enrollment, or the patient was prone to severe bleeding or coagulation dysfunction, or was undergoing thrombolytic therapy Has active autoimmune disease requiring systemic treatment within the two years before enrollment , especially those with immunosuppressive drugs, who were unable to control or who needed large amounts of immunosuppressive drugs to control the disease, excluding topical glucose-corticosteroids or systemic use, and prednisone less than 10 milligrams per day Has central nervous system disease with symptoms, such as primary brain tumor, stroke, epilepsy, etc. Patients who have undergone central nervous system or known brain metastases Has acute or severe hepatitis infection, or a severe bacterial or bacterial infection in an active or clinically poorly controlled, or with congenital or acquired immune deficiency such human immunodeficiency virus (HIV) infected Has previous allogeneic stem cell or parenchymal organ transplantation, including after liver transplantation Has history of allergies to drugs involved in this study Women who are pregnant or lactating, or who do not want to use contraception during the trial.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tingbo Liang

Phone

+8613666676128

liangtingbo@zju.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Xueli Bai

Phone

+8613757166693

shirleybai@zju.edu.cn

Facility Information:

Facility Name

the First Affiliated Hospital, School of Medicine, Zhejiang University

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310003

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Liang TingBo, MD, PHD

Phone

086-571-87236688

liangtingbo@zju.edu.cn

12. IPD Sharing Statement

Learn more about this trial

Combination of Anti-PD-1 Antibody and Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma

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