Bladder Cancer
Conditions
Brief summary
Researchers are looking for new ways to treat muscle-invasive bladder cancer (MIBC). MIBC is a type of bladder cancer that has spread into the muscle layer of the bladder but has not spread to other distant parts of the body. The usual treatment for MIBC is surgery to remove the bladder but some people choose to have other treatments, such as chemoradiotherapy (CRT), instead of surgery so they can keep their bladder. Researchers want to know if giving 2 trial treatments with CRT can treat MIBC. One trial treatment is called sacituzumab tirumotecan (sac-TMT) and the other trial treatment is called subcutaneous (SC) pembrolizumab (or pembrolizumab and berahyaluronidase alfa). The main goal of this trial is to learn if participants who receive sac-TMT, SC pembrolizumab, and CRT live longer without their cancer growing, spreading, or coming back compared to those who receive CRT alone.
Interventions
BIOLOGICALSac-TMT
IV infusion
BIOLOGICALPembrolizumab and Berahyaluronidase alfa
Pembrolizumab coformulated with berahyaluronidase alfa administered as a SC injection
DRUGCisplatin
IV infusion administered at 35 mg/m\^2 weekly for up to 6 doses during RT
DRUG5-FU
IV infusion administered at 500 mg/m\^2 on Days 1 to 5 and Days 22 to 26 during RT
DRUGMMC
IV infusion administered at 12 mg/m\^2 on Day 1 during RT
DRUGCapecitabine
Oral dose administered at 825 mg/m\^2 twice daily during RT
DRUGGemcitabine
IV infusion administered at 27 mg/m\^2 twice weekly for up to 12 doses during RT
RADIATIONConventional Radiotherapy
External beam radiation administered per global clinical guidelines (64 Gy at 2 Gy/fraction over approximately 6.5 weeks)
RADIATIONHypofractionated radiotherapy
External beam radiation administered per global clinical guidelines (55 Gy at 2.75 Gy/fraction over approximately 4 weeks)
Participants receive rescue medications at the investigator's discretion, per approved product label. Rescue medications include pegfilgrastim (or equivalent), H1 receptor antagonist, H2 receptor antagonist, acetaminophen (or equivalent), dexamethasone (or equivalent), steroid mouthwash (dexamethasone or equivalent).
Sponsors
Merck Sharp & Dohme LLC
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
The main inclusion criteria include but are not limited to the following: * Has a diagnosis of muscle-invasive bladder cancer (MIBC) (cT2-T4aN0-N1) * Has clinically nonmetastatic bladder cancer (N0-N1M0) * Is either ineligible for radical cystectomy or has opted for bladder preservation and is planned to receive chemoradiotherapy (CRT) * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | Up to approximately 60 months | EFS is defined as the time from randomization to the first occurrence of any of the following events, as assessed by blinded independent central review (BICR): residual/recurrent MIBC, or locoregional disease, or distant metastases as assessed by imaging and/or biopsy results, or death from any cause. The EFS for all participants will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 90 months | OS is defined as the time from randomization to death due to any cause. The OS for all participants will be presented. |
| Distant Metastasis-Free Survival (DMFS) | Up to approximately 90 months | DMFS is defined as the time from randomization to the first occurrence of any of the following events, as assessed by BICR: distant metastatic disease as assessed by imaging and/or biopsy results, or death due to any cause. DMFS for all participants will be presented. |
| Bladder Intact (BI)-EFS | Up to approximately 90 months | BI-EFS is defined as the time from randomization to the first occurrence of any of the following events: residual/recurrent MIBC, or locoregional disease, or distant metastases as assessed by imaging and/or biopsy results, or radical cystectomy, or death from any cause. The BI-EFS for all participants will be presented. |
| Time to Occurrence of Non-Muscle-Invasive Bladder Cancer (NMIBC) | Up to approximately 90 months | Time to occurrence of NMIBC, defined as the time from randomization to the first occurrence of NMIBC (\<T2 disease in bladder) after CRT as assessed by biopsy results, will be presented for all participants. |
| Disease-Specific Survival | Up to approximately 90 months | DSS is defined as the time from randomization to death due to bladder cancer. The DSS for all participants will be presented. |
| Rate of Radical Cystectomy | Up to approximately 90 months | Rate of radical cystectomy is defined as the percentage of participants who undergo radical cystectomy at any time after randomization, for any reason. Rate of radical cystectomy for all participants will be presented. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 90 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported. |
| Number of Participants Who Discontinue Study Intervention Due to an AE | Up to approximately 90 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study intervention due to an AE will be reported. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed