RC48 Combined With Toripalimab and Radiotherapy for Bladder Sparing Treatment in MIBC

Radiotherapy Clinical Trial

Official title: RC48 Combined With PD-1 and Radiotherapy as Bladdersparing Therapy in Patients With Muscular Infiltrating Bladder Uroepithelial Carcinoma With Limited HER-2 Expression Following Maximum Electrical Resection or Partial Cystectomy

Status Recruiting

Clinical Trial Summary

This is a prospective, open, single-center clinical study of RC48 combined with PD-1 and radiotherapy as bladder-preserving therapy in patients with muscular invasive bladder uroepithelial carcinoma with high HER-2 expression (IHC 2+ or 3+). The study was conducted in accordance with the Good Practice for Clinical Trials of Pharmaceutical Products (GCP). Six patients were enrolled in this study. Each patient received RC48 injection [2.0 mg/kg, Q2W, iv] and Toripalimab injection [3mg/kg, Q2W, iv] for 1~2 cycles, and radiotherapy at the second or third cycle. The total dose of bladder irradiation field was greater than 50Gy (about 30 times), and the safety monitoring of the subjects was conducted within 28 days after receiving the study drug treatment for the first time. Adverse events were graded using the National Cancer Institute (NCI) Standard for the Assessment of Common Terminology for Adverse Events (CTCAE) Version 5.0 guidelines, and the occurrence of DLT in patients was observed. If the subject does not complete the safety assessment for the tolerance observation period for non-dose tolerance reasons, a new subject will be replaced.

Clinical Trial Description

This is a prospective, open, single-center clinical study of RC48 in combination with PD-1 and radiotherapy as bladder-preserving therapy in patients with muscular invasive bladder uroepithelial carcinoma with high HER-2 expression (IHC 2+ or 3+). The study was conducted in accordance with the Good Practice for Clinical Trials of Pharmaceutical Products (GCP).

Subjects undergo maximum transurethral electrocystotomy (TURBT) or partial cystectomy, imaging diagnosis, and pre-treatment biological samples of blood, urine, and biopsy tissue. The researchers determined that localized invasive bladder cancer with high HER-2 expression could be treated with bladder conserving therapy with maximum TURBT. Patients will receive RC48 combined with PD-1 and radiotherapy after TURBT surgery. Subjects should receive RC48 combined with PD-1 every two weeks for 12 treatment cycles and radiotherapy (bladder irradiation field greater than 50Gy). After completion of the above treatment, tumor site pathology, imaging, and exfoliation cytology are obtained with diagnostic TURBT for tumor evaluation to determine complete remission, and the first tumor efficacy evaluation is performed after completion of radiotherapy (12 weeks after treatment) and every 12 weeks after completion of radiotherapy. Patients with radiotherapy intolerance (as assessed by the investigator) were discontinued directly.

Adverse events will be monitored during the study period and graded using the National Cancer Institute's (NCI) Standards for the Assessment of Adverse Events in General Terminology (CTCAE) Version 5.0 guidelines. The safety assessment was carried out after 28 days.

Subjects who discontinue medication for reasons other than disease progression will be followed for post-treatment disease status until subjects begin other antitumor therapy, develop disease progression, withdraw informed consent, die, or end of the study, whichever occurs first. All subjects will be followed up via outpatient cystoscopy (every 3 months within 1 year of withdrawal and every 6 months after 1 year) until subject's death, withdrawal of informed consent, or the end of the study, whichever occurs first.

Participation in this study will require participants to submit a TURBT tumor tissue specimen or a newly obtained tumor lesion biopsy from prior untreated radiation therapy for biomarker and efficacy correlation evaluation.

Blood and urine samples from patients will be collected during the treatment to explore potential biomarkers correlated to the treatment efficacy and patient response. ;

Related Conditions & MeSH terms

• Muscle Invasive Bladder Cancer
• PD-1
• Radiotherapy
• Urinary Bladder Neoplasms

• NCT number: NCT05979740
• Study type: Interventional
• Source: RenJi Hospital
• Contact: Haige Chen
• Phone: 02168383575
• Email: kirbyhaige@aliyun.com
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2023
• Completion date: February 13, 2024