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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04413734
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : June 4, 2020
Sponsor:
Information provided by (Responsible Party):
TingBo Liang, Zhejiang University

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.

Condition or disease Intervention/treatment Phase
Intrahepatic Cholangiocarcinoma by AJCC V8 Stage Drug: Combination therapy Drug: Mono-chemotherapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination of Anti-PD-1 Antibody and Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Exploratory Clinical Trial
Actual Study Start Date : April 22, 2020
Estimated Primary Completion Date : April 22, 2022
Estimated Study Completion Date : April 22, 2024


Arm Intervention/treatment
Experimental: Triprilumab in combination with chemotherapy of GP
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 .
Drug: Combination therapy
Triprilumab by intravenous infusion accompanying with Gemcitabine plus Cisplatin
Other Names:
  • Triprilumab
  • Immunotherapy
  • Anti-PD-1 therapy

Active Comparator: Mono-chemotherapy of GP
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.
Drug: Mono-chemotherapy
Gemcitabine plus Cisplatin by intravenous infusion
Other Name: Gemcitabine Injection plus Cisplatin Injection




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Observation period 48 months ]
    Time from first randomization to the first documented disease progression or death due to any cause, whichever occurs first.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 48 months ]
    Overall survival is defined as the time from randomization to death due to any cause.

  2. Objective Response Rate (ORR) per RECIST 1.1 [ Time Frame: Up to 48 months ]
    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

  3. Disease Control Rate(DCR) [ Time Frame: Up to 48 months ]
    DCR is defined as the percentage of participants who have a confirmed Complete Response or Partial Response as assessed by RECIST 1.1

  4. Myopathologic response(MPR) [ Time Frame: Up to 48 months ]
    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

  5. Conversion surgical resection(R0) rate [ Time Frame: Up to 48 months ]
    the ratio of patients successfully converted into radical surgical resection by the treatment plan, in which the margin of the liver is negative

  6. Adverse Events (AE) [ Time Frame: Up to 48 months ]
    Safety evaluation was done continuously during treatment by using CTCAE 5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04413734


Contacts
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Contact: Tingbo Liang +8613666676128 liangtingbo@zju.edu.cn
Contact: Xueli Bai +8613757166693 shirleybai@zju.edu.cn

Locations
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China, Zhejiang
the First Affiliated Hospital, School of Medicine, Zhejiang University Recruiting
Hangzhou, Zhejiang, China, 310003
Contact: Liang TingBo, MD, PHD    086-571-87236688    liangtingbo@zju.edu.cn   
Sponsors and Collaborators
Zhejiang University
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Responsible Party: TingBo Liang, Clinical Professor, Zhejiang University
ClinicalTrials.gov Identifier: NCT04413734    
Other Study ID Numbers: CISLD-9
First Posted: June 4, 2020    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by TingBo Liang, Zhejiang University:
Intrahepatic Cholangiocarcinoma
Immunotherapy
anti-programmed-death-1 antibody
Additional relevant MeSH terms:
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Cholangiocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Carcinoma
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs