Bladder (Urothelial, Transitional Cell) Cancer, NMIBC
Conditions
Keywords
NMIBC, disitamab vedotin, HER2, BCG
Brief summary
The purpose of this study is to learn about the safety and effects of the study medicine (Disitamab Vedotin) in people with non-muscle invasive bladder cancer. This study is seeking participants whose bladder cancer is still in early stages, has not spread outside of the bladder, has been removed with surgery, and is high risk. Each participant was assigned to one of two study treatment groups: One group is given Disitamab Vedotin and BCG.The second group is given BCG only and will not receive Disitamab Vedotin.
Detailed description
HERO: A Phase III Randomized Controlled Trial of Disitamab Vedotin (DV) Combined with Bacillus Calmette-Guérin (BCG) in BCG-Naïve Patients with HER2-Expressing, High-Risk Non-Muscle-Invasive Bladder Cancer This Phase 3, open-label, randomized, controlled clinical trial will enroll approximately 182 patients, who will be assigned in a 1:1 ratio to one of two treatment groups: Group A: Disitamab Vedotin plus BCG (induction and maintenance therapy) Group B: BCG alone (induction and maintenance therapy) The study is designed to demonstrate the superiority of Disitamab Vedotin combined with BCG (during both induction and maintenance phases) over BCG alone in prolonging event-free survival (EFS) among BCG-naïve participants with high-risk, HER2-expressing non-muscle invasive bladder cancer.
Interventions
DRUGActive Comparator: BCG induction and maintenance
Drug: Bacillus Calmette-Guerin Immunotherapy treatment approved by NMPA for patients with high-risk non-muscle invasive bladder cancer Other Names: BCG
DRUGDV + BCG induction and maintenance
Drug: Disitamab vedotin(RC48) •An antibody-drug conjugates (ADCs) targeting HER2, has been approved in China for chemotherapy-refractory advanced UC with HER2-expression. Other Names: • RC48, DV Drug: Bacillus Calmette-Guerin Immunotherapy treatment approved by NMPA for patients with high-risk non-muscle invasive bladder cancer Other Names: BCG
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years. 2. Histologically confirmed high-risk, non-muscle-invasive urothelial carcinoma of the bladder (UCC) (with \>50% urothelial carcinoma as the predominant histological component), defined by the presence of any of the following: a. T1 tumor; b. High-grade Ta tumor; c. Carcinoma in situ (CIS). 3. Complete resection of all Ta/T1 papillary lesions (including patients with concomitant CIS). The most recent Transurethral Resection of Bladder Tumor (TURBT) must have been performed within 12 weeks prior to randomization. A second TURBT was required if indicated per current local applicable guidelines. 4. HER2 expression (IHC 1+/2+/3+) as confirmed by immunohistochemistry (IHC) testing at the local institution's pathology department. 5. Unwillingness or ineligibility to undergo radical cystectomy. 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2. 7. Signed informed consent form (ICF).
Exclusion criteria
1. Histologically confirmed evidence of muscle-invasive (T2 or higher), locally advanced, or metastatic urothelial carcinoma, or the presence of concurrent extravesical non-muscle-invasive urothelial carcinoma. 2. Histopathological findings of pure small cell carcinoma, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder. 3. History of upper tract urothelial carcinoma (except for cases with no recurrence within 2 years following radical treatment for UTUC). 4. Prior therapy with any other type of HER2-targeted inhibitor. 5. Major surgery within 2 weeks prior to randomization. 6. Any other condition that, in the investigator's judgment, would make the patient unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival | 55 months after first participant randomized | Event free survival is defined as the time from randomization to date of EFS event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Randomization up to 60 months from last participant randomized | Overall survival is defined as the time from the date of randomization to the date of death due to any cause. |
| Complete response rate at 6m/12m in participants with CIS at randomization | Randomization up to 12 months from last participant randomized | Complete response (CR) rate defined as the proportion of participants in the analysis population with CR. |
| Disease-specific survival | Randomization up to 60 months from last participant randomized | Disease specific survival (DSS) is defined as the time from randomization to death resulting from bladder cancer. |
| Health-related quality of life as measured by EORTC QLQ-C30 | Randomization up to 60 months from last participant randomized | Health-related quality of life as measured by EORTC QLQ-C30 |
| Health-related quality of life as measured by EORTC QLQ-NMIBC24 | Randomization up to 60 months from last participant randomized | EORTC-QLQ-NMIBC24 has 24 items which can be grouped into 6 subscales: urinary symptoms (7 items), malaise (2 items), future worries (4 items), bloating/flatulence (2 items), sexual functioning (2 items), and male sexual issues (2 items). The NMIBC24 also assesses intravesical treatment, female sexual issues, sexual intimacy, risk of contaminating a partner, and sexual enjoyment (1 item each). |
Countries
China
Contacts
CONTACTYi jun Shen, M.D.
Outcome results
None listed