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Multicenter Phase 2 Study of Envafolimab in Biliary Tract Cancers

Primary Purpose

Biliary Tract Neoplasms

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Envafolimab plus Gemcitabine&Cisplatin
Gemcitabine&Cisplatin
Sponsored by
3D Medicines (Sichuan) Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Biliary Tract Neoplasms

Eligibility Criteria

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

Inclusion Criteria:

  1. Be ≥ 18 years of age;
  2. Subjects must have a histopathological or cytological diagnosis of locally advanced or metastatic gallbladder cancer (GBC) or cholangiocarcinoma (CCA);
  3. Subjects who have not received prior systemic therapy for advanced disease or who have received adjuvant or neoadjuvant chemotherapy in one regimen and relapsed > 6 months after the end of chemotherapy can be enrolled;
  4. Child-Pugh liver function rating: class A (5-6 points) and better class B (7 points) (see Appendix 3);
  5. ECOG PS score 0 or 1 (see Appendix 1);
  6. Expected survival ≥ 12 weeks;
  7. Subjects with at least one measurable lesion (RECIST 1.1 criteria, see Appendix 2);
  8. Subject must have adequate major organ and bone marrow functions (no blood transfusion and no use of hematopoietic growth factor within 14 days before the first dose of study treatment):

1) Hematology: neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, and hemoglobin ≥ 90 g/L; 2) International normalized ratio (INR) ≤ 1.5 × upper limit of normal (ULN) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 3) Liver function: serum total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels >1.5 ULN; Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) ≤ 2.5 × ULN OR ≤ 5 × ULN for subjects with liver metastases; 4) Renal function: serum creatinine ≤ 1.5 x ULN and creatinine clearance (CCr) > 60 mL/min (assessed with Cockcroft-Gault formula, see Appendix 6); 5) Normal cardiac function with left ventricular ejection fraction (LVEF) ≥ 50% by two-dimensional echocardiography.

9. Subjects must fully understand the study, voluntarily participate, and sign the informed consent form (ICF).

Exclusion Criteria:

  1. Has participated in another clinical trials of other investigational drugs or investigational devices within 4 weeks prior to the first dose of investigational product treatment (palliative radiotherapy for bone metastases completed at least 2 weeks prior to investigational product treatment is allowed);
  2. The investigator assesses liver metastases as 50% or more of the total liver volume;
  3. Has ascites requiring drainage or treatment with diuretics, or pleural or pericardial effusion requiring drainage and/or associated with symptoms of tachypnea within 4 weeks prior to the first dose of investigational product treatment;
  4. Has biliary obstruction with clinical intervention that has not resolved or requires anti-infective therapy as judged by the investigator 14 days prior to the first dose of investigational product treatment;
  5. Has prior liver transplantation;
  6. Has known active brain metastases or spinal cord compression; subjects with previously treated brain metastases may be enrolled if their clinical condition is stable and radiographic evidence shows no disease progression within 4 weeks prior to the first dose of investigational product treatment, and corticosteroid therapy is not required within 4 weeks prior to the first dose of investigational product treatment;
  7. Has a known additional malignant tumor in the past 5 years (except for skin basal cell or squamous cell carcinoma, or cervical, breast and other carcinoma in situ after radical surgery);
  8. Has received major surgical procedures (except biopsy) or incomplete healing of surgical wound within 4 weeks prior to the first dose of investigational product treatment;
  9. Has any unresolved toxicity (CTCAE Grade ≥ 2) from prior anti-tumor therapy, except for alopecia or Grade 2 peripheral neuropathy or other laboratory abnormalities that are not clinically significant as assessed by the investigator;
  10. Has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism that is stable on hormone replacement will not be excluded from the study;
  11. Has known history of HIV, or active bacterial or fungal infection requiring systemic treatment within 14 days prior to the first dose of investigational product treatment;
  12. Has history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, symptomatic interstitial lung disease or presence of active pneumonitis on chest CT scan within 4 weeks before the first dose of investigational product treatment;
  13. Has active hepatitis B (HBsAg positive and HBV-DNA ≥ 104 copies/mL) or hepatitis C (HCV antibody positive and HCV-RNA quantitative test results greater than the lower limit of detection);
  14. Has a history or current evidence of clinically significant cardiovascular diseases, including but not limited to acute myocardial infarction, severe/unstable angina, acute ischemic/hemorrhagic stroke, congestive heart failure (≥ New York Heart Association Class II, see Appendix 4) within 6 months prior to enrollment; arrhythmias requiring treatment with other antiarrhythmic drugs in addition to β-blockers or digoxin; repeat QTcF interval > 450 milliseconds (ms) on ECG (see Appendix 5); hypertension not well controlled with antihypertensive drug therapy (systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg);
  15. Be receiving therapeutic doses of warfarin (low-dose warfarin ≤ 2 mg/day is allowed); or receiving antiplatelet anticoagulant therapy (aspirin doses ≤ 300 mg/day and clopidogrel doses ≤ 75 mg/day are allowed);
  16. Has received immunosuppressive drugs within 4 weeks prior to the first dose of investigational product treatment, excluding topical corticosteroids or systemic prednisone ≤ 10 mg/day or equivalent doses of other corticosteroids;
  17. Has received live vaccines within 4 weeks before the first dose of investigational product treatment or plan to receive it during the study;
  18. Has history of severe allergic reactions to chimeric or human antibodies or fusion proteins, or known allergies to biological products produced with Chinese hamster ovary cells or any component of envafolimab; known or suspected allergy to the chemotherapeutic drug gemcitabine/cisplatin and its components;
  19. Be pregnant or breastfeeding;
  20. Be childbearing potential but unwilling to accept effective contraceptive measures;
  21. Any other disease, metabolic disorder or laboratory abnormalities, that the investigator considers that the subject is not suitable for the investigational product treatment, or will affect the interpretation of the study results, or put the subject at high risk.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Envafolimb

    Gemcitabine&Cisplatin

    Arm Description

    Envafolimab plus Gemcitabine&Cisplatin Envafolimab: 300 mg on Day 1 of each cycle, subcutaneous injection. Every 21 days is a treatment cycle. Gemcitabine (GEM): 1000 mg/m2 body surface area (BSA) administered on Days 1 and 8 of each cycle. Every 21 days is a treatment cycle with a maximum of 8 cycles. Cisplatin (CIS): 25 mg/m2 body surface area (BSA) administered on Days 1 and 8 of each cycle. Every 21 days is a treatment cycle with a maximum of 8 cycles.

    Gemcitabine (GEM): 1000 mg/m2 body surface area (BSA) administered on Days 1 and 8 of each cycle. Every 21 days is a treatment cycle with a maximum of 8 cycles. Cisplatin (CIS): 25 mg/m2 body surface area (BSA) administered on Days 1 and 8 of each cycle. Every 21 days is a treatment cycle with a maximum of 8 cycles.

    Outcomes

    Primary Outcome Measures

    Progression-free survival (PFS)
    To evaluate the progression-free survival (PFS) of envafolimab in combination with gemcitabine plus cisplatin (GemCis) versus first-line treatment of GemCis in patients with advanced biliary tract cancers (BTC).

    Secondary Outcome Measures

    Overall survival (OS)
    To evaluate the overall survival (OS) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;
    Objective response rate(ORR)
    To evaluate the objective response rate (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;
    Duration of response (DoR)
    To evaluate the duration of response (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;
    Disease control rate (DCR)
    To evaluate the disease control rate (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;

    Full Information

    First Posted
    May 27, 2021
    Last Updated
    July 12, 2023
    Sponsor
    3D Medicines (Sichuan) Co., Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04910386
    Brief Title
    Multicenter Phase 2 Study of Envafolimab in Biliary Tract Cancers
    Official Title
    A Randomized, Open-Label, Multicenter Phase 2 Study of Envafolimab in Combination With Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin as the First-line Treatment in Patients With Locally Advanced or Metastatic Biliary Tract Cancers
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 1, 2024 (Anticipated)
    Primary Completion Date
    June 1, 2026 (Anticipated)
    Study Completion Date
    June 1, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    3D Medicines (Sichuan) Co., Ltd.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a Randomized, Open-Label, Multicenter Phase 2 Study to access the efficacy and safety of Envafolimab in Combination with Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin as the First-line Treatment in Patients with Locally Advanced or Metastatic Biliary Tract Cancers

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    126 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Envafolimb
    Arm Type
    Experimental
    Arm Description
    Envafolimab plus Gemcitabine&Cisplatin Envafolimab: 300 mg on Day 1 of each cycle, subcutaneous injection. Every 21 days is a treatment cycle. Gemcitabine (GEM): 1000 mg/m2 body surface area (BSA) administered on Days 1 and 8 of each cycle. Every 21 days is a treatment cycle with a maximum of 8 cycles. Cisplatin (CIS): 25 mg/m2 body surface area (BSA) administered on Days 1 and 8 of each cycle. Every 21 days is a treatment cycle with a maximum of 8 cycles.
    Arm Title
    Gemcitabine&Cisplatin
    Arm Type
    Active Comparator
    Arm Description
    Gemcitabine (GEM): 1000 mg/m2 body surface area (BSA) administered on Days 1 and 8 of each cycle. Every 21 days is a treatment cycle with a maximum of 8 cycles. Cisplatin (CIS): 25 mg/m2 body surface area (BSA) administered on Days 1 and 8 of each cycle. Every 21 days is a treatment cycle with a maximum of 8 cycles.
    Intervention Type
    Drug
    Intervention Name(s)
    Envafolimab plus Gemcitabine&Cisplatin
    Intervention Description
    Envafolimab a programmed death ligand immune check inhibitor Per Investigator decision
    Intervention Type
    Drug
    Intervention Name(s)
    Gemcitabine&Cisplatin
    Intervention Description
    The standard of care for the patients with unresectable/metastatic biliary tract cancer
    Primary Outcome Measure Information:
    Title
    Progression-free survival (PFS)
    Description
    To evaluate the progression-free survival (PFS) of envafolimab in combination with gemcitabine plus cisplatin (GemCis) versus first-line treatment of GemCis in patients with advanced biliary tract cancers (BTC).
    Time Frame
    Observed by 12 weeks
    Secondary Outcome Measure Information:
    Title
    Overall survival (OS)
    Description
    To evaluate the overall survival (OS) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;
    Time Frame
    Observed by 12 weeks after progressive disease or end of treatment
    Title
    Objective response rate(ORR)
    Description
    To evaluate the objective response rate (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;
    Time Frame
    Observed by 12 weeks
    Title
    Duration of response (DoR)
    Description
    To evaluate the duration of response (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;
    Time Frame
    Observed by 12 weeks
    Title
    Disease control rate (DCR)
    Description
    To evaluate the disease control rate (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;
    Time Frame
    Observed by 12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Be ≥ 18 years of age; Subjects must have a histopathological or cytological diagnosis of locally advanced or metastatic gallbladder cancer (GBC) or cholangiocarcinoma (CCA); Subjects who have not received prior systemic therapy for advanced disease or who have received adjuvant or neoadjuvant chemotherapy in one regimen and relapsed > 6 months after the end of chemotherapy can be enrolled; Child-Pugh liver function rating: class A (5-6 points) and better class B (7 points) (see Appendix 3); ECOG PS score 0 or 1 (see Appendix 1); Expected survival ≥ 12 weeks; Subjects with at least one measurable lesion (RECIST 1.1 criteria, see Appendix 2); Subject must have adequate major organ and bone marrow functions (no blood transfusion and no use of hematopoietic growth factor within 14 days before the first dose of study treatment): 1) Hematology: neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, and hemoglobin ≥ 90 g/L; 2) International normalized ratio (INR) ≤ 1.5 × upper limit of normal (ULN) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 3) Liver function: serum total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels >1.5 ULN; Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) ≤ 2.5 × ULN OR ≤ 5 × ULN for subjects with liver metastases; 4) Renal function: serum creatinine ≤ 1.5 x ULN and creatinine clearance (CCr) > 60 mL/min (assessed with Cockcroft-Gault formula, see Appendix 6); 5) Normal cardiac function with left ventricular ejection fraction (LVEF) ≥ 50% by two-dimensional echocardiography. 9. Subjects must fully understand the study, voluntarily participate, and sign the informed consent form (ICF). Exclusion Criteria: Has participated in another clinical trials of other investigational drugs or investigational devices within 4 weeks prior to the first dose of investigational product treatment (palliative radiotherapy for bone metastases completed at least 2 weeks prior to investigational product treatment is allowed); The investigator assesses liver metastases as 50% or more of the total liver volume; Has ascites requiring drainage or treatment with diuretics, or pleural or pericardial effusion requiring drainage and/or associated with symptoms of tachypnea within 4 weeks prior to the first dose of investigational product treatment; Has biliary obstruction with clinical intervention that has not resolved or requires anti-infective therapy as judged by the investigator 14 days prior to the first dose of investigational product treatment; Has prior liver transplantation; Has known active brain metastases or spinal cord compression; subjects with previously treated brain metastases may be enrolled if their clinical condition is stable and radiographic evidence shows no disease progression within 4 weeks prior to the first dose of investigational product treatment, and corticosteroid therapy is not required within 4 weeks prior to the first dose of investigational product treatment; Has a known additional malignant tumor in the past 5 years (except for skin basal cell or squamous cell carcinoma, or cervical, breast and other carcinoma in situ after radical surgery); Has received major surgical procedures (except biopsy) or incomplete healing of surgical wound within 4 weeks prior to the first dose of investigational product treatment; Has any unresolved toxicity (CTCAE Grade ≥ 2) from prior anti-tumor therapy, except for alopecia or Grade 2 peripheral neuropathy or other laboratory abnormalities that are not clinically significant as assessed by the investigator; Has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism that is stable on hormone replacement will not be excluded from the study; Has known history of HIV, or active bacterial or fungal infection requiring systemic treatment within 14 days prior to the first dose of investigational product treatment; Has history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, symptomatic interstitial lung disease or presence of active pneumonitis on chest CT scan within 4 weeks before the first dose of investigational product treatment; Has active hepatitis B (HBsAg positive and HBV-DNA ≥ 104 copies/mL) or hepatitis C (HCV antibody positive and HCV-RNA quantitative test results greater than the lower limit of detection); Has a history or current evidence of clinically significant cardiovascular diseases, including but not limited to acute myocardial infarction, severe/unstable angina, acute ischemic/hemorrhagic stroke, congestive heart failure (≥ New York Heart Association Class II, see Appendix 4) within 6 months prior to enrollment; arrhythmias requiring treatment with other antiarrhythmic drugs in addition to β-blockers or digoxin; repeat QTcF interval > 450 milliseconds (ms) on ECG (see Appendix 5); hypertension not well controlled with antihypertensive drug therapy (systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg); Be receiving therapeutic doses of warfarin (low-dose warfarin ≤ 2 mg/day is allowed); or receiving antiplatelet anticoagulant therapy (aspirin doses ≤ 300 mg/day and clopidogrel doses ≤ 75 mg/day are allowed); Has received immunosuppressive drugs within 4 weeks prior to the first dose of investigational product treatment, excluding topical corticosteroids or systemic prednisone ≤ 10 mg/day or equivalent doses of other corticosteroids; Has received live vaccines within 4 weeks before the first dose of investigational product treatment or plan to receive it during the study; Has history of severe allergic reactions to chimeric or human antibodies or fusion proteins, or known allergies to biological products produced with Chinese hamster ovary cells or any component of envafolimab; known or suspected allergy to the chemotherapeutic drug gemcitabine/cisplatin and its components; Be pregnant or breastfeeding; Be childbearing potential but unwilling to accept effective contraceptive measures; Any other disease, metabolic disorder or laboratory abnormalities, that the investigator considers that the subject is not suitable for the investigational product treatment, or will affect the interpretation of the study results, or put the subject at high risk.

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Multicenter Phase 2 Study of Envafolimab in Biliary Tract Cancers

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