A Prospective, Single-arm, Exploratory Study on the Efficacy and Safety of Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin in Patients With Neuroendocrine Bladder Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Adebrelimab
- Conditions
- Neuroendocrine Carcinoma of the Bladder
- Sponsor
- RenJi Hospital
- Enrollment
- 22
- Locations
- 5
- Primary Endpoint
- Pathologic complete response (ypCR) at cystectomy
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males or females aged ≥18 years and ≤75 years.
- •ECOG performance status of 0 -
- •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.
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.
Arms & Interventions
Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy
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: Adebrelimab
Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy
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: Etoposide
Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy
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: Cisplatin
Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy
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: Radical Cystectomy
Outcomes
Primary Outcomes
Pathologic complete response (ypCR) at cystectomy
Time Frame: At the time of radical cystectomy (within 18 weeks of the first dose)
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
Time Frame: Up to 2 years
The number of participants experiencing treatment-related adverse events, defined by NCI CTCAE 5.0
Secondary Outcomes
- Pathologic downstage at cystectomy(At the time of radical cystectomy (within 18 weeks of the first dose))
- Progression Free Survival(Up to 2 years)
- Cancer Specific Survival(Up to 2 years)
- Overall Survival(Up to 2 years)