Clinical trial NCT06091124: Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin in Neuroendocrine Bladder Carcinoma
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neuroendocrine Carcinoma of the Bladder
Bladder Cancer
Keywords: Neuroendocrine Carcinoma of the Bladder
Neoadjuvant Therapy
Adebrelimab
Etoposide
Cisplatin
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2023-10-19
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

  1. Blood routine examination:

     HB≥90 g/L; ANC≥1.5×109 /L; PLT≥100×109 /L.
  2. 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.

Primary outcomes:
measure: Pathologic complete response (ypCR) at cystectomy
timeFrame: At the time of radical cystectomy (within 18 weeks of the first dose)
measure: Safety and tolerability of combination therapy and radical cystectomy
timeFrame: Up to 2 years
Secondary outcomes:
measure: Pathologic downstage at cystectomy
timeFrame: At the time of radical cystectomy (within 18 weeks of the first dose)
measure: Progression Free Survival
timeFrame: Up to 2 years
measure: Cancer Specific Survival
timeFrame: Up to 2 years
measure: Overall Survival
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ren Ji Hospital
state: Shanghai
Study officials:
References: