Disitamab Vedotin Plus Intravesical Mitomycin C in HER2-Expressing Intermediate- to High-Risk Non-Muscle-Invasive Bladder Cancer

Official title

Disitamab Vedotin Plus Intravesical Mitomycin C in HER2-Expressing Medium-high Risk Non-Muscle-Invasive Bladder Cancer: A Phase II Clinical Trial

Overview

This study aims to evaluate the efficacy and safety of intravenous administration of vedacitinib combined with intravesical instillation of mitomycin in treating patients with high-risk NMIBC with HER2 expression. The goal is to provide a new treatment option for NMIBC patients, reduce the risk of tumor recurrence, decrease the proportion of radical bladder surgery, and improve the quality of life of patients.

Interventions

• Drug Disitamab Vedotin
  Disitamab Vedotin injection: 2.0 mg/kg, every two weeks, treatment lasts for 8 to 12 cycles
• Drug Mitomycin C (MMC)
  Mitomycin bladder intravesical instillation: 40mg per dose. Instill immediately after surgery, then once a week thereafter. The induction chemotherapy instillation lasts for 8 times. Subsequently, it is instilled once a month for a total of 10 months for maintenance chemotherapy.

Primary outcome measures

• 1-year disease-free survival rate(1-year DFS rate) [Time frame: At 12 months after the first study treatment.]

Secondary outcome measures (3)

• Disease-free survival [Time frame: From drug combination to the first documented recurrence, disease progression, death from any cause, or last follow-up, assessed up to 12 months.]
• Overall Survival（OS） [Time frame: From the date of first study treatment to the date of death from any cause or last known follow-up, whichever occurred first, assessed up to 12 months.]
• Incidence and Severity of Treatment-emergent Adverse Events [Time frame: From the date of first study treatment until 30 days after the last dose of study treatment, assessed up to 12 months.]

Eligibility criteria

Inclusion criteria

• Voluntary participation, signing a written informed consent form;
• The age on the date of signing the informed consent form should be no less than 18 years old, regardless of gender;
• The subjects have completed the standard TURBT procedure before signing the informed consent form, and no obvious residual tumor lesions were found in the surgical field;
• The postoperative pathology clearly diagnosed as non-muscle-invasive bladder cancer, and the main tissue component was more than 50% urothelial carcinoma (transitional cell carcinoma);
• The subjects were classified into the intermediate-risk or high-risk group according to the risk classification for NMIBC;
• Tumor tissue samples for TURBT must be provided, along with the required relevant pathological reports. Fresh surgical tissues or pathological slides can be sent for examination as well;
• The patients were intolerant to BCG or did not accept the BCG infusion treatment plan;
• Before treatment, HER2 detection was conducted on the resection specimens in the laboratory: The IHC results confirmed HER2 expression (defined as: IHC 1+, 2+ or 3+);
• Clinical non-metastatic bladder cancer (N0, M0) was determined by abdominal computed tomography (CT).

Exclusion criteria

• History of muscle-invasive bladder cancer or metastatic bladder cancer before treatment;History of muscle-invasive bladder cancer or metastatic bladder cancer before treatment;
• Imaging results within 3 months before treatment indicated lymph node or other site/organ metastasis;
• Imaging results within 3 months before treatment indicated the presence of other urinary system tumors;
• Received other systemic anti-cancer treatments within 3 weeks before treatment, including chemotherapy, biological therapy, immunotherapy, targeted therapy, endocrine therapy, and/or investigational drug therapy;
• Received bladder radiotherapy for urothelial carcinoma before treatment;
• Known to have anaphylaxis or delayed allergic reaction to certain components of vedacitinib or similar drugs;
• Within the 3 days prior to the first infusion, the following conditions had not yet been alleviated to CTCAE grade 1:Uncontrolled acute or chronic infections, such as pneumonia, biliary tract infections;Hepatitis B and Hepatitis C infections; dyspnea;Acute or chronic kidney injury; nephrotic syndrome; bladder perforation; urinary tract obstruction;
• NYHA rating of 3 or 4;
• Symptoms and signs related to cardiovascular diseases: including myocardial infarction, congestive heart failure, arrhythmia, etc.;
• Known cerebrovascular accidents;
• History of autoimmune diseases (such as inflammatory bowel disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, hemolytic anemia, rheumatoid arthritis, etc.);
• Known positive HIV serology, Hepatitis C infection and/or Hepatitis B (HepBsAg or core antibody positive and responding after antiviral treatment for Hepatitis B, except for these patients: these patients are allowed to participate in this study; Note: Patients with negative HepBsAg at screening)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanxi Provincial Cancer Hospital — Taiyuan

Identifiers

NCT: NCT07646145 · KY2024066

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗