Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin in Neuroendocrine Bladder Carcinoma

NCT06091124 | Recruiting Phase 2

• 1 other identifier: IIT-2023-0177
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

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.

Conditions

Neuroendocrine Carcinoma of the Bladder; Bladder Cancer

Keywords

Neuroendocrine Carcinoma of the Bladder; Neoadjuvant Therapy; Adebrelimab; Etoposide; Cisplatin

Outcome Measures

Primary Outcomes (2)

• 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 .

  At the time of radical cystectomy (within 18 weeks of the first dose)

• Safety and tolerability of combination therapy and radical cystectomy

  The number of participants experiencing treatment-related adverse events, defined by NCI CTCAE 5.0

  Up to 2 years

Secondary Outcomes (4)

• 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

Study Arms (1)

Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy

EXPERIMENTAL

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.

Drug: Adebrelimab; Drug: Etoposide; Drug: Cisplatin; Procedure: Radical Cystectomy

Interventions

Radical Cystectomy PROCEDURE

Radical cystectomy should be performed within 4-6 weeks after completion of last dose

Also known as: RC

Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy

Adebrelimab DRUG

Adebrelimab 1200 mg IV on Day 1, once every 3 weeks for up to 4 cycles (each cycle = 21 days)

Also known as: SHR-1316, HTI-1088

Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy

Etoposide DRUG

Etoposide 0.1g IV on Days 1-3, once every 3 weeks for up to 4 cycles (each cycle = 21 days)

Also known as: VP-16, Vepesid, Toposar

Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy

Cisplatin DRUG

Cisplatin 35mg/m2 IV on Days 1-2, once every 3 weeks for up to 4 cycles (each cycle = 21 days)

Also known as: Cis-Diaminedichloroplatinum, CDDP

Neoadjuvant Adebrelimab Plus Etoposide and Cisplatin Followed by Radical Cystectomy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (5)

Jiangsu Province Hospital

Nanjing, Jiangsu, China

RECRUITING

The First Affiliated Hospital of Xi'an Jiao Tong University

Xi'an, Shaanxi, China

RECRUITING

RenJi Hospital

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

West China Hospital

Chengdu, Sichuan, China

RECRUITING

The Second Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, China

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Etoposide; Cisplatin; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Central Study Contacts

Haige Chen, M.D.

CONTACT

86 17521674856; rjbladder@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2023
• First Posted: October 19, 2023
• Study Start: November 16, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)