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Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin in Neuroendocrine Bladder Carcinoma (RJBLC-NEBC001)

Primary Purpose

Neuroendocrine Carcinoma of the Bladder, Bladder Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Adebrelimab
Etoposide
Cisplatin
Radical Cystectomy
Sponsored by
RenJi Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Carcinoma of the Bladder focused on measuring Neuroendocrine Carcinoma of the Bladder, Neoadjuvant Therapy, Adebrelimab, Etoposide, Cisplatin

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Males or females aged ≥18 years and ≤75 years. ECOG performance status of 0 - 2. Histologically confirmed invasive neuroendocrine carcinoma with or without urothelial carcinoma, with a neuroendocrine carcinoma component of >50%; Formalin-fixed paraffin-embedded (FFPE) specimens (preferred) or at least 15 unstained, freshly cut, continuous slides should be submitted with related pathology reports prior to study enrollment. If fewer than 15 slides are available, patients may still be eligible for enrollment after confirmation by the principal investigator. If a tumor tissue section is not available, the tumor tissue must be obtained from the biopsy performed at the time of screening. Clinical stage T1-T4a N0 M0 (CT/MRI ± PET/CT) If the clinical stage is T1-4a N1-3 M0, it needs to be judged by the investigator. If cystectomy can still be performed, participants can be included in the study. Expected survival longer 3 months. Normal function of vital organs (14 days prior to enrollment). Meet the following criteria: Blood routine examination: HB≥90 g/L; ANC≥1.5×109 /L; PLT≥100×109 /L. No functional organic disease: T-BIL≤1.5×ULN (upper limit of normal); ALT and AST≤2.5 x ULN; Serum creatinine ≤2×ULN, or endogenous creatinine clearance > 20 mL /min (Cockcroft-Gault formula); International Standardized ratio (INR), activated partial thromboplastin time (aPTT) : ≤1.5× ULN. Fertile males or females must use a highly effective contraceptive approach (such as oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicides) during the trial and continue contraception for 12 months after the end of treatment. Participants who voluntarily join the study, sign informed consent, have good compliance, and cooperate with follow-up. Exclusion Criteria: Prior anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapy. Prior drug therapy for cancer, except: Intravesical chemotherapy or immunotherapy ended at least 1 week before the start of study. Prior radiotherapy for bladder cancer. Participants allergic to adebrelimab and its components. Participants who have received other antitumor therapy or immunomodulatory therapy (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks before the start of study treatment, or have not recovered from previous toxicity (except for 2 degree alopecia and 1 degree neurotoxicity). Pregnant or lactating females. HIV Positive. Participants with active hepatitis B or C: For participants with HBsAg or HBcAb positive and detected HBV DNA copy number (quantitative detection limit is 500IU/ml, or reach the positive value of copy number detected by the research center), HBV DNA must be tested for screening in such patients. Participants positive for HCV antibodies were enrolled in this study only if the PCR test for HCV RNA was negative. Active tuberculosis. Active autoimmune disease that requires systemic treatment within the past 2 years (such as disease-modulating drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for renal or pituitary insufficiency) are accepted. Other serious, uncontrolled medical conditions that may affect protocol adherence or interfere with interpretation of results. These include active opportunistic or progressive (severe) infections, uncontrolled diabetes, cardiovascular disease (heart failure as defined by the New York Heart Association scale as grade III or IV, cardiac conduction block above grade II, myocardial infarction within the last 6 months, unstable arrhythmia or unstable angina, cerebral infarction within the last 3 months, etc.), or pulmonary disease (interstitial pneumonia, Obstructive pulmonary disease and a history of symptomatic bronchospasm). Those who received live vaccine within 4 weeks prior to the start of treatment (seasonal influenza vaccines are usually inactivated and therefore permitted for use). Intranasal vaccines are live vaccines, so they are not allowed to be used). Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation. History of psychotropic substance abuse and cannot abstain or have a history of mental disorders. Pleural fluid or ascites associated with clinical symptoms or requiring symptomatic management. Participants with other malignancies that have not healed in the past 5 years, excluding apparently cured malignancies, or curable cancers such as basal or squamous cell skin cancer, localized low-risk prostate cancer, cervical carcinoma in situ, or breast carcinoma in situ. Concomitant upper tract urothelial carcinoma (pelvis and ureter urothelial carcinoma). Other severe, acute, or chronic medical or psychiatric disorders, or laboratory abnormalities that, in the investigator's opinion, may increase the risks associated with study participation or that may interfere with the interpretation of the study results.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy

    Arm Description

    The study population will include male and female patients over the age of 18 with invasive (cT1-cT4) neuroendocrine carcinoma of the bladder, with or without urothelial component (neuroendocrine component should be >50%). Patients with resectable N1-3 disease (judged by investigators) are eligible. Patients should be fit to undergo cystectomy with normal function of vital organs. Participants will be intravenously treated with adebrelimab (1200mg, day 1) in combination with etoposide (0.1g, day 1-3) and cisplatin (35mg/m2, day 1-2) every 21 days for a maximum of 4 cycles. Radical cystectomy, lymph node dissection and urine diversion will be performed after the completion of therapy.

    Outcomes

    Primary Outcome Measures

    Pathologic complete response (ypCR) at cystectomy
    The number of participants with pathologic complete responses (ypCR) at cystectomy. Pathologic complete response is defined as post-treatment stages of T0N0M0 .
    Safety and tolerability of combination therapy and radical cystectomy
    The number of participants experiencing treatment-related adverse events, defined by NCI CTCAE 5.0

    Secondary Outcome Measures

    Pathologic downstage at cystectomy
    The number of participants with pathological downstage at cystectomy. Pathologic downstage response is defined as downstaged T stage or N stage at cystectomy .
    Progression Free Survival
    Defined by time from day of first treatment to disease progression
    Cancer Specific Survival
    Defined by time from day of first treatment to death of the disease
    Overall Survival
    Defined by time from day of first treatment to death

    Full Information

    First Posted
    October 14, 2023
    Last Updated
    October 14, 2023
    Sponsor
    RenJi Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06091124
    Brief Title
    Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin in Neuroendocrine Bladder Carcinoma
    Acronym
    RJBLC-NEBC001
    Official Title
    A Prospective, Single-arm, Exploratory Study on the Efficacy and Safety of Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin in Patients With Neuroendocrine Bladder Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 1, 2023 (Anticipated)
    Primary Completion Date
    December 31, 2024 (Anticipated)
    Study Completion Date
    December 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    RenJi Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    The goal of this clinical trial is to learn about the efficacy and safety of neoadjuvant adebrelimab plus etoposide and cisplatin in patients with neuroendocrine bladder carcinoma. The main questions it aims to answer are: The pathologic complete response rate at radical cystectomy Safety and tolerability of combination therapy Participants will be treated with a combination therapy of adebrelimab, etoposide, and cisplatin before radical cystectomy, with a maximum of 4 cycles.
    Detailed Description
    This is an prospective, single-arm, open-label clinical study of neoadjuvant adebrelimab in combination with etoposide and cisplatin in patients with neuroendocrine bladder carcinoma. Approximately 22 participants will be enrolled in this study to evaluate the efficacy and safety of neoadjuvant adebrelimab, cisplatin and etoposide. The study population will include male and female patients over the age of 18 with invasive (cT1-cT4) neuroendocrine carcinoma of the bladder, with or without urothelial component (neuroendocrine component should be >50%). Patients with resectable N1-3 disease (judged by investigators) are eligible. Patients should be fit to undergo cystectomy with normal function of vital organs. Participants will be intravenously treated with adebrelimab (1200mg, day 1) in combination with etoposide (0.1g, day 1-3) and cisplatin (35mg/m2, day 1-2) every 21 days for a maximum of 4 cycles. Radical cystectomy, lymph node dissection and urine diversion will be performed after the completion of therapy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Neuroendocrine Carcinoma of the Bladder, Bladder Cancer
    Keywords
    Neuroendocrine Carcinoma of the Bladder, Neoadjuvant Therapy, Adebrelimab, Etoposide, Cisplatin

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    22 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy
    Arm Type
    Experimental
    Arm Description
    The study population will include male and female patients over the age of 18 with invasive (cT1-cT4) neuroendocrine carcinoma of the bladder, with or without urothelial component (neuroendocrine component should be >50%). Patients with resectable N1-3 disease (judged by investigators) are eligible. Patients should be fit to undergo cystectomy with normal function of vital organs. Participants will be intravenously treated with adebrelimab (1200mg, day 1) in combination with etoposide (0.1g, day 1-3) and cisplatin (35mg/m2, day 1-2) every 21 days for a maximum of 4 cycles. Radical cystectomy, lymph node dissection and urine diversion will be performed after the completion of therapy.
    Intervention Type
    Drug
    Intervention Name(s)
    Adebrelimab
    Other Intervention Name(s)
    SHR-1316, HTI-1088
    Intervention Description
    Adebrelimab 1200 mg IV on Day 1, once every 3 weeks for up to 4 cycles (each cycle = 21 days)
    Intervention Type
    Drug
    Intervention Name(s)
    Etoposide
    Other Intervention Name(s)
    VP-16, Vepesid, Toposar
    Intervention Description
    Etoposide 0.1g IV on Days 1-3, once every 3 weeks for up to 4 cycles (each cycle = 21 days)
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin
    Other Intervention Name(s)
    Cis-Diaminedichloroplatinum, CDDP
    Intervention Description
    Cisplatin 35mg/m2 IV on Days 1-2, once every 3 weeks for up to 4 cycles (each cycle = 21 days)
    Intervention Type
    Procedure
    Intervention Name(s)
    Radical Cystectomy
    Other Intervention Name(s)
    RC
    Intervention Description
    Radical cystectomy should be performed within 4-6 weeks after completion of last dose
    Primary Outcome Measure Information:
    Title
    Pathologic complete response (ypCR) at cystectomy
    Description
    The number of participants with pathologic complete responses (ypCR) at cystectomy. Pathologic complete response is defined as post-treatment stages of T0N0M0 .
    Time Frame
    At the time of radical cystectomy (within 18 weeks of the first dose)
    Title
    Safety and tolerability of combination therapy and radical cystectomy
    Description
    The number of participants experiencing treatment-related adverse events, defined by NCI CTCAE 5.0
    Time Frame
    Up to 2 years
    Secondary Outcome Measure Information:
    Title
    Pathologic downstage at cystectomy
    Description
    The number of participants with pathological downstage at cystectomy. Pathologic downstage response is defined as downstaged T stage or N stage at cystectomy .
    Time Frame
    At the time of radical cystectomy (within 18 weeks of the first dose)
    Title
    Progression Free Survival
    Description
    Defined by time from day of first treatment to disease progression
    Time Frame
    Up to 2 years
    Title
    Cancer Specific Survival
    Description
    Defined by time from day of first treatment to death of the disease
    Time Frame
    Up to 2 years
    Title
    Overall Survival
    Description
    Defined by time from day of first treatment to death
    Time Frame
    Up to 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Males or females aged ≥18 years and ≤75 years. ECOG performance status of 0 - 2. Histologically confirmed invasive neuroendocrine carcinoma with or without urothelial carcinoma, with a neuroendocrine carcinoma component of >50%; Formalin-fixed paraffin-embedded (FFPE) specimens (preferred) or at least 15 unstained, freshly cut, continuous slides should be submitted with related pathology reports prior to study enrollment. If fewer than 15 slides are available, patients may still be eligible for enrollment after confirmation by the principal investigator. If a tumor tissue section is not available, the tumor tissue must be obtained from the biopsy performed at the time of screening. Clinical stage T1-T4a N0 M0 (CT/MRI ± PET/CT) If the clinical stage is T1-4a N1-3 M0, it needs to be judged by the investigator. If cystectomy can still be performed, participants can be included in the study. Expected survival longer 3 months. Normal function of vital organs (14 days prior to enrollment). Meet the following criteria: Blood routine examination: HB≥90 g/L; ANC≥1.5×109 /L; PLT≥100×109 /L. No functional organic disease: T-BIL≤1.5×ULN (upper limit of normal); ALT and AST≤2.5 x ULN; Serum creatinine ≤2×ULN, or endogenous creatinine clearance > 20 mL /min (Cockcroft-Gault formula); International Standardized ratio (INR), activated partial thromboplastin time (aPTT) : ≤1.5× ULN. Fertile males or females must use a highly effective contraceptive approach (such as oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicides) during the trial and continue contraception for 12 months after the end of treatment. Participants who voluntarily join the study, sign informed consent, have good compliance, and cooperate with follow-up. Exclusion Criteria: Prior anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapy. Prior drug therapy for cancer, except: Intravesical chemotherapy or immunotherapy ended at least 1 week before the start of study. Prior radiotherapy for bladder cancer. Participants allergic to adebrelimab and its components. Participants who have received other antitumor therapy or immunomodulatory therapy (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks before the start of study treatment, or have not recovered from previous toxicity (except for 2 degree alopecia and 1 degree neurotoxicity). Pregnant or lactating females. HIV Positive. Participants with active hepatitis B or C: For participants with HBsAg or HBcAb positive and detected HBV DNA copy number (quantitative detection limit is 500IU/ml, or reach the positive value of copy number detected by the research center), HBV DNA must be tested for screening in such patients. Participants positive for HCV antibodies were enrolled in this study only if the PCR test for HCV RNA was negative. Active tuberculosis. Active autoimmune disease that requires systemic treatment within the past 2 years (such as disease-modulating drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for renal or pituitary insufficiency) are accepted. Other serious, uncontrolled medical conditions that may affect protocol adherence or interfere with interpretation of results. These include active opportunistic or progressive (severe) infections, uncontrolled diabetes, cardiovascular disease (heart failure as defined by the New York Heart Association scale as grade III or IV, cardiac conduction block above grade II, myocardial infarction within the last 6 months, unstable arrhythmia or unstable angina, cerebral infarction within the last 3 months, etc.), or pulmonary disease (interstitial pneumonia, Obstructive pulmonary disease and a history of symptomatic bronchospasm). Those who received live vaccine within 4 weeks prior to the start of treatment (seasonal influenza vaccines are usually inactivated and therefore permitted for use). Intranasal vaccines are live vaccines, so they are not allowed to be used). Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation. History of psychotropic substance abuse and cannot abstain or have a history of mental disorders. Pleural fluid or ascites associated with clinical symptoms or requiring symptomatic management. Participants with other malignancies that have not healed in the past 5 years, excluding apparently cured malignancies, or curable cancers such as basal or squamous cell skin cancer, localized low-risk prostate cancer, cervical carcinoma in situ, or breast carcinoma in situ. Concomitant upper tract urothelial carcinoma (pelvis and ureter urothelial carcinoma). Other severe, acute, or chronic medical or psychiatric disorders, or laboratory abnormalities that, in the investigator's opinion, may increase the risks associated with study participation or that may interfere with the interpretation of the study results.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Haige Chen
    Phone
    02168383575
    Email
    kirbyhaige@aliyun.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin in Neuroendocrine Bladder Carcinoma

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