Tislelizumab(Anti PD-1), Lenvatinib and GEMOX Transformation in the Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer

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Brief Title

Tislelizumab(Anti PD-1), Lenvatinib and GEMOX Transformation in the Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer

Official Title

A Single-arm, Multi-center, Phase II Study of Tislelizumab, Lenvatinib and GEMOX Transformation in the Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer

Brief Summary

      The aim of this study is to assess the R0 resection rate of tislelizumab combined with
      Lenvatinib and Gemox chemotherapy in the conversion therapy of potentially resectable locally
      advanced BTC.
    

Detailed Description

      Translational therapy refers to methods such as chemotherapy, radiotherapy, immunotherapy,
      targeted and combined therapy to shrink tumors, reduce tumor biological behavior, and achieve
      secondary resection. The success rate of transformation depends on the objective response
      rate of the treatment method (Objective response rate, ORR). The latest review showed that
      132 patients with unresectable ICC had undergone chemotherapy, chemoembolization,
      radiotherapy embolization or combination therapy, and 27 patients received downgrade
      resection. The research of our group using PD-1 antibody combined with lenvatinib and Gemox
      chemotherapy in the first-line treatment of unresectable advanced cholangiocarcinoma
      (NCT03951597, 2020ESMO, 2021ASCO) showed that the ORR was 80% and the disease control rate
      (DCR) It reached 93.3% (28/30), of which 3 cases underwent successful radical resection after
      downstage. These data suggest that PD1 monoclonal antibody combined with lenvatinib and Gemox
      chemotherapy may be an ideal conversion therapy for patients with potentially resectable
      advanced biliary system tumors, but there is currently no evidence-based basis.

      This study explores the efficacy and safety of PD1 monoclonal antibody combined with
      Lenvatinib and Gemox chemotherapy in potentially resectable advanced BTC conversion therapy.
      It has certain clinical significance in order to increase the R0 surgical resection rate of
      BTC patients and improve patient survival.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

R0 resection rate

Secondary Outcome

 ORR

Condition

Biliary Tract Cancer

Intervention

PD-1+Lenvatinib+GEMOX

Study Arms / Comparison Groups

 PD-1 antibody +Lenvatinib+Gemox
Description:  Tilelizumab 200mg, d1 Q3W Lenvatinib 8mg, po, qd, Gemox chemotherapy Gemcitabine 1000mg/m2, d1, 8, Q3W, + oxaliplatin 85mg/m2 d1, Q3W

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

40

Start Date

December 12, 2021

Completion Date

October 1, 2025

Primary Completion Date

October 1, 2022

Eligibility Criteria

        Inclusion Criteria:

          -  1. Male or female aged 18-70 2. The patient must sign an informed consent form before
             joining the group, understand and be willing to sign a written informed consent form
             3. Potentially resectable locally advanced BTC (including ICC, PBDT and GBC) confirmed
             by histology or cytology, agree to provide previously stored tumor tissue specimens or
             fresh biopsy tumor lesions for biomarker detection 4. Local progress, failure to
             achieve R0 resection, and no distant metastasis, with potential resection 5. At least
             one measurable lesion (RECIST 1.1) 6. Have never received systemic treatment for
             biliary tumors in the past 7. Eastern Cooperative Oncology Group (ECOG) performance
             status score ECOG PS 0-1 8. Liver function classification is Child-Pugh A 9. The bone
             marrow, liver and kidneys are fully functional and reach the following clinical
             laboratory evaluation standards within 7 days before treatment:

        Blood indicators:

        Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet ≥ 90 × 109/L, hemoglobin ≥ 90 g/L.

        Liver function indicators:

        AST and ALT are both ≤3×ULN (upper limit of normal value); total bilirubin ≤1.5×ULN

        Kidney function indicators:

        Serum creatinine≤1.5×ULN

        Coagulation index:

        International normalized ratio (INR) ≤ 1.2 or prothrombin time (PT) ≤ 1.2×ULN

        Obstructive jaundice, after PTCD or ERCP treatment, if the liver function indicators meet
        the requirements for entry, it can be considered for entry:

        10. If the subject has HBV or HCV infection, the following conditions must be met:

        For inactive/asymptomatic carriers of HBV, chronic, or active HBV:

        HBV deoxyribonucleic acid (DNA) <2000 copies/mL during the screening period. Remarks:
        Patients with HBV DNA>2000 copies/mL should be treated according to treatment guidelines.
        Patients who received antiviral drug treatment at the time of screening should have HBV-DNA
        <2000 copies/mL and continue treatment during the study period.

        For subjects infected with HCV:

        If the infection is confirmed based on the detectable HCV ribonucleic acid RNA, such
        subjects cannot be included in the group.

        11. If you are a fertile woman (that is, physically capable of getting pregnant), you must
        agree to take effective contraceptive measures during the study period and within 120 days
        after the last administration, and have urine within 7 days before the first study drug
        administration Or the serum pregnancy test is negative.

        12. If you are a non-sterilized male, you need to agree to take effective contraceptive
        measures during the study period and 120 days after the last dose.

        13. Life expectancy ≥ 3 months

        Exclusion Criteria:

          -  1. Diagnosed as mixed type of periampullary carcinoma, hepatocellular carcinoma and
             cholangiocarcinoma 2. Have received systemic treatment for biliary tumors in the past
             3. Have previously received gemcitabine-based chemotherapy or TKI therapy or any tumor
             immunotherapy (for example, PD-1/L1 inhibitors, CTLA-4 inhibitors, etc.) 4. Have a
             history of severe hypersensitivity to other monoclonal antibodies 5. Allergy to
             tislelizumab or any of its excipients; allergy to oxaliplatin and any of its
             excipients; allergy to gemcitabine and any of its excipients; allergy to lenvatinib
             and any of its excipients 6. The presence of pericardial effusion, uncontrollable
             pleural effusion or clinically obvious ascites within 7 days before treatment is
             defined as meeting the following criteria: (a) Ascites can be detected by physical
             examination during screening, or (b) during screening, Ascites requires puncture
             fluid.

             7. There is no clinical evidence of portal hypertension with esophageal or gastric
             varices within 6 months before starting treatment.

             8. Any bleeding or thrombotic disease or any anticoagulant (such as warfarin or
             similar drugs) that needs to monitor the international standardized ratio during
             treatment within 6 months before the start of treatment 9. Has suffered from any
             malignant tumors, except for the BTC studied in this clinical trial and locally
             recurring cancers that have been cured (such as resected basal cell or squamous cell
             skin cancer, superficial bladder cancer, cervical or breast cancer) Carcinoma in situ,
             occult carcinoma of the thyroid).

             10. Any known central nervous system metastasis and/or leptomeningeal disease have
             been present before treatment.

             11. A history of any active immunodeficiency or autoimmune disease and/or any
             immunodeficiency or autoimmune disease that may recur at the time of screening

        Note: Subjects with the following diseases can be selected:

        Type I diabetes Hypothyroidism (if only hormone replacement therapy can be used to control)
        Controlled celiac disease Skin diseases that do not require systemic treatment (eg
        vitiligo, psoriasis, hair loss) Any other disease that will not recur without external
        triggers 12. Any disease requiring systemic treatment with corticosteroids (dose higher
        than 10mg/day of prednisone or equivalent doses of similar drugs) or other
        immunosuppressive agents in the 14 days before treatment.

        Remarks: Subjects who have currently or previously used any of the following steroid
        regimens can be selected:

        In the absence of active autoimmune diseases, adrenaline replacement steroids are allowed
        (prednisone ≤10mg/day or equivalent dose of similar drugs) Local, ophthalmic,
        intra-articular, intranasal and inhaled corticosteroids with minimal systemic absorption
        Prophylactic short-term use (≤7 days) corticosteroids (for example, allergy to contrast
        agents) or for the treatment of non-autoimmune conditions (for example, delayed
        hypersensitivity reactions caused by contact allergens) 13. There is a history of
        interstitial lung disease or non-infectious pneumonia.

        14. Any serious chronic infection or active infection (excluding viral hepatitis) that
        requires systemic antibacterial, antifungal or antiviral therapy (such as tuberculosis)
        before starting treatment.

        15. The electrocardiogram during screening showed that the QT interval (QTc) corrected
        according to the heart rate (corrected according to the Fridericia method) exceeded 450
        msec.

        Note: If any patient finds that the QTc interval exceeds 450 msec during the first ECG
        examination, the ECG will be repeated to confirm the result.

        16. Any of the following cardiovascular risk factors: Cardiogenic chest pain in the 28 days
        before treatment, defined as moderate pain that restricts daily activities (ADL)
        Symptomatic pulmonary embolism occurred within 28 days before treatment A history of acute
        myocardial infarction occurred within 6 months before treatment.

        Any history of heart failure reaching New York Heart Association grade III or IV within 6
        months of treatment Ventricular arrhythmia of grade ≥2 occurred within 6 months before
        treatment Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within
        6 months before treatment.

        17. Have received organ transplantation or hematopoietic stem cell transplantation (HSCT)
        or any major surgery within 28 days before treatment.

        18. Known mental or substance abuse disorders that may interfere with test compliance.

        19. Live vaccine has been vaccinated 28 days before treatment. Note: Seasonal influenza
        vaccines are generally inactivated influenza vaccines and are allowed to be used.

        20. Known history of human immunodeficiency virus infection (HIV) or syphilis infection.

        21. The history or evidence of any disease, treatment, or laboratory abnormality that may
        confuse the test results, interfere with the participation of the subject during the entire
        trial, or the main investigator believes that it does not meet the subject's best benefit.

        22. Currently participating in and receiving treatment, or participating in or
        participating in other drug or device research within 4 weeks after the first
        administration of the research drug.

        23. From the screening visit to 120 days after the last drug administration, pregnancy or
        breastfeeding, or expectation of pregnancy or childbirth within the planned duration of the
        trial.

        24. The investigator judges that the compliance is not good, or there are other conditions
        that make the patients unsuitable to participate in this trial.

        25. There are various medical contraindications that prevent the use of enhanced imaging
        (CT or MRI).

        26. There are surgical contraindications, and the researchers believe that it is not
        suitable for surgical patients.
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Jia Fan, +8615021519215, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT05156788

Organization ID

BTC-2021


Responsible Party

Sponsor

Study Sponsor

Shanghai Zhongshan Hospital


Study Sponsor

Jia Fan, Principal Investigator, Shanghai Zhongshan Hospital


Verification Date

December 2021