Treating Muscle-invasive Bladder Cancer With A Non-surgical Method Consisting of Anti-PD-1 Therapy and Chemoradiation

NCT05975307 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 2023-FXY-068
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this Phase 2 trial is to evaluate a non-surgical bladder-preserving treatment mode which consists of neoadjuvant chemotherapy plus anti-programmed cell death protein 1 (anti-PD-1) therapy followed by radiotherapy plus concurrent anti-PD-1 therapy. The main questions it aims to answer are: (i) whether the anti-PD-1 antibody, toripalimab, is effective in treating muscle-invasive bladder cancer (MIBC), when combined with chemoradiation; (ii) whether toripalimab is safe in combination with chemoradiation. Participants will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy plus 2 cycles of concurrent toripalimab.

Conditions

Muscle-Invasive Bladder Carcinoma; Programmed Cell Death Protein 1 Inhibitor; Radiotherapy

Keywords

Bladder Cancer; Programmed Cell Death Protein 1 Inhibitor; Radiotherapy; Chemotherapy; Bladder Preservation

Outcome Measures

Primary Outcomes (1)

• Clinical complete response (cCR) rate

  The percentage of the cases attaining cCR of primary tumor and regional lymph nodes (confirmed by radiologic examinations, such as thoraco-bdominal computed tomography, pelvic magnetic resonance imaging, and multipoint biopsy under cystoscopy)

  When the eligible patients complete the treatment and followed-up for half a year

Secondary Outcomes (7)

• Overall survival (OS)

  When the eligible patients complete the treatment and followed-up for 1 and 2 years

• Bladder-intact event-free survival (BI-EFS)

  When the eligible patients complete the treatment and followed-up for 1 and 2 years

• Disease-free survival (DFS)

  When the eligible patients complete the treatment and followed-up for 1 and 2 years

• Local recurrence (LR) rate

  When the eligible patients complete the treatment and followed-up for 1 and 2 years

• Incidence of grade 3/4 (G3/4) toxicities

  Once a week during treatment, and once per 3 months after treatment, until the last follow-up (2 years after treatment)

Study Arms (1)

Toripalimab plus chemoradiation

EXPERIMENTAL

This study has only single arm in which the patients will receive neoadjuvant chemotherapy plus anti-PD-1 therapy (toripalimab), followed by radiotherapy plus concurrent anti-PD-1 therapy

Drug: Toripalimab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Radiation: Intensity-modulated radiation therapy

Interventions

Toripalimab DRUG

The patients in this arm will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Toripalimab: 240 mg on Day 1, every 3 weeks, totally 3 and 2 cycles in the neoadjuvant and concurrent phases, respectively.

Also known as: JS001

Toripalimab plus chemoradiation

Gemcitabine DRUG

The patients in this arm will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Gemcitabine: 1 g/m2 on Days 1 and 8, repeated every 3 weeks, totally 3 cycles.

Toripalimab plus chemoradiation

Cisplatin DRUG

The patients in this arm will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Cisplatin: Used when creatinine clearance rate ≥ 40 ml/min, 37.5 mg/m2 on Days 1 and 2, repeated every 3 weeks, totally 3 cycles.

Toripalimab plus chemoradiation

Carboplatin DRUG

The patients in this arm will receive 3 cycles of induction treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Cisplatin: Used when creatinine clearance rate \< 40 ml/min, area under curve = 2 on Days 1 and 2, repeated every 3 weeks, totally 3 cycles.

Toripalimab plus chemoradiation

Intensity-modulated radiation therapy RADIATION

The patients in this arm will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Radiotherapy: performed by using the technique of intensity-modulated radiation therapy, with a total dose of 65 and 45 Gy for the gross tumor and lymphatic drainage regions.

Toripalimab plus chemoradiation

Eligibility Criteria

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

You may qualify if:

• Pathologically diagnosed bladder malignant tumor via biopsy
• Urothelial carcinoma as the primary histological component
• Pretreatment clinical TNM stage as T2-4aN0M0 or T1-4aN1-2M0 (UICC TNM staging classification, version 8)
• Age between 18 and 75 years old
• Karnofsky performance score ≥ 70
• Creatinine clearance rate ≥ 30 ml/min

You may not qualify if:

• Simultaneous tumors of the urethra or upper urinary tract
• Existence of small cell cancer component
• Uncontrolled tuberculosis, viral hepatitis or AIDS
• Autoimmune or mental diseases
• Severe cardiac, renal, hepatic or hematopoietic dysfunctions unsuitable for chemotherapy, radiotherapy or immune checkpoint inhibiting therapy
• Prior history of other malignancies within 5 years, except cured cervical carcinoma in situ and skin basal cell carcinoma
• Prior history of pelvic radiotherapy or chemotherapy
• Poor adherence to regular follow-up (cystoscopy, CT, MRI, etc.)
• Pregnant or lactating women
• Treatment with glucocorticoid or immunosuppressive drugs within 1 month
• Other situations for which the investigators consider a patient inappropriate to participate

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Cancer Center, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

toripalimab; Gemcitabine; Cisplatin; Carboplatin; Radiotherapy, Intensity-Modulated

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)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Yuanhong Gao, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director of the Department of Radiation Oncology, Cancer Center

Model Details: This phase 2 trial is an open-label, single-arm, non-comparative trial, in which all eligible patients will receive neoadjuvant chemotherapy plus toripalimab, followed by radiotherapy plus concurrent toripalimab.

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: August 3, 2023
• Study Start: December 1, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2029
• Last Updated: December 1, 2025

Record last verified: 2025-11

Locations

CN (1)