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HAIC With FOLFOX and Bevacizumab Plus Intravenous Toripalimab for Advanced BTC

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: NCT04217954
Recruitment Status : Not yet recruiting
First Posted : January 6, 2020
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
Xiaodong Wang, MD, Peking University

Brief Summary:

Biliary tract cancer includes gallbladder carcinoma and cholangiocarcinoma. Recently, the incidence of the biliary cancer is increasing, especially in China.

The prognosis of biliary tract cancer is poor. Only 20% patients are candidate to be performed surgery, and the median overall survival of the advanced biliary tract cancer is less than 6 months. Gemcitabine plus cisplatin were consider as the first-line chemotherapy regimen for advanced biliary tract cancer for many years. The objective response rate (ORR) after it is 26.1% and the median overall survival is less than 1 year.

Two years ago, a phase II study of hepatic arterial infusion chemotherapy with oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma finished in Peking University Cancer Hospital. The ORR in the study achieved 67.6% and the median overall survival achieved 20.5 months. In 2019, a retrospective study in Peking University Cancer Hospital showed that hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil and bevacizumab for patients with unresectable intrahepatic cholangiocarcinoma has a ORR of 63.5% and the median overall survival achieved 14.5 months.

Programmed death-1 (PD-1) checkpoint inhibitor, like Toripalimab, can block the bind of PD-1 and PD-L1/PD-L2, then influence the immune response and recover the function of cytotoxic T lymphocytes. There are some studies indicate that the targeted agent of anti-angiogenesis, like bevacizumab, can adjust the immune microenvironment of the tumor to enhance the efficacy of the immunotherapy.

Likewise, the agents of chemotherapy can enhance the antigenicity of the tumor, and increase the ratio of CD8+ T cells in tumor microenvironment by the pattern of damage-associated molecular pattern (DAMP) so that have synergistic effect with PD-1 checkpoint inhibitor.

Recently, 9 patients with advanced biliary tract cancer received hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil and bevacizumab plus intravenous Toripalimab in our center, and 3 of them lost to follow-up. Among the other 6 patients, the ORR and disease control rate achieved 83.3% and 100%, respectively.

In this study, investigators want to research the efficacy and safety of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil and bevacizumab plus intravenous Toripalimab for advance biliary tract cancer.


Condition or disease Intervention/treatment Phase
Advanced Biliary Tract Cancer Other: oxaliplatin, 5-fluorouracil and bevacizumab plus Toripalimab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hepatic Arterial Infusion Chemotherapy With Oxaliplatin, 5-fluorouracil and Bevacizumab Plus Intravenous Toripalimab for Advanced Biliary Tract Cancer
Estimated Study Start Date : May 15, 2020
Estimated Primary Completion Date : June 15, 2022
Estimated Study Completion Date : May 15, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: FOLFOX plus Bev plus Toripalimab
the patients enrolled in this arm would receive hepatic arterial infusion with oxaliplatin, 5-fluorouracil and bevacizumab plus intravenous Toripalimab
Other: oxaliplatin, 5-fluorouracil and bevacizumab plus Toripalimab
hepatic arterial infusion with oxaliplatin, 5-fluorouracil and bevacizumab plus intravenous Toripalimab




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: date from the first treatment to disease get progression, assessed at least 2 months ]
    date from the first treatment to disease get progression


Secondary Outcome Measures :
  1. overall survival [ Time Frame: date from the first treatment to patients dead or lost to follow-up, assessed at least 6 months ]
    date from the first treatment to patients dead or lost to follow-up



Information from the National Library of Medicine

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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:

  • 1. Biliary tract cancer proved by histology or cytology, patients proved by histology must check the status of the expression of PD-1 by immunohistochemical technology.

    2. Unresectable biliary tract cancer, including gallbladder cancer, intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma, decided by hepatobiliary doctor and radiologist.

    3.Age from 18 years old to 80 years old. 4. the performance of Eastern Cooperative Oncology Group (ECOG) <2 5. Child-Pugh A or Child-Pugh B (≥ grade 7). 6. Expectant survival time ≥ 3 months. 7. Baseline blood count test and blood biochemical must meet following criteria:

    1. Hemoglobin ≥90 g/L;
    2. Absolute neutrophil count ≥ 1.5×10^9/L;
    3. Blood platelet count ≥100×10^9/L;
    4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times of upper limit of normal (ULN);
    5. Total bilirubin ≤ 2 times of ULN;
    6. Serum creatinine ≤ 1.5 times of ULN;
    7. Albumin ≥ 30 g/L. 8. Patients sign informed consent.

      Exclusion Criteria:

  • 1. Distal cholangiocarcinoma. 2. Allergic to contrast agent. 3. Pregnant or lactational. 4. Allergic to 5-fluorouracil, or have metabolic disorder of 5-fluorouracil. 5. More than 80 years old. 6. Previous systematic chemotherapy or radiotherapy. 7. Child-Pugh C or Child-Pugh B ( ≥ grade 8). 8. Multiple metastasis beyond liver. 9. Coinstantaneous malignant hydrothorax or ascites. 10. History of organ transplantation ( including bone marrow auto-transplantation and peripheral stem cell transplantation).

    11. Coinstantaneous infection and need anti infection therapy. 12. Hepatitis B virus DNA load ≥ 100 IU/ml ( patients whose hepatitis B virus DNA load decreased to < 100 IU/ml after anti virus therapy could be enrolled).

    13. Coinstantaneous peripheral nervous system disorder or with history of obvious mental disorder and central nervous system disorder.

    14. Diagnosed other kinds of malignant within 5 years, except for non-melanoma skin cancer and carcinoma in situ of cervix.

    15. Without legal capacity. 16. Impact the study because of medical or ethical reasons. 17. Uncorrectable coagulation disorder. 18. Obvious abnormal in ECG or obvious clinical symptoms of heart disease, like congestive heart failure (CHF), coronary heart disease with obvious clinical symptoms, unmanageable arrhythmia and hypertension.

    19. History of myocardial infarction within 12 months, or Grade III or IV of heart function.

    20. Severe liver disease ( like cirrhosis ), renal disease, respiratory disease, unmanageable diabetes or other kinds of systematic disease.


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): NCT04217954


Contacts
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Contact: Xiaodong Wang, MD 0086-18611586227 tigat@126.com

Sponsors and Collaborators
Peking University
Investigators
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Study Director: Xiaodong Wang, MD Department of Interventional Radiology, Peking University Cancer Hospital
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Responsible Party: Xiaodong Wang, MD, Deputy Director of Department of Interventional Therapy, Peking University Cancer Hospital, Peking University
ClinicalTrials.gov Identifier: NCT04217954    
Other Study ID Numbers: FIBTC
First Posted: January 6, 2020    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: signed informed consent with patients

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Bevacizumab
Fluorouracil
Oxaliplatin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors