Advanced Urothelial Carcinoma, Immunotherapy, Probiotics
Conditions
Brief summary
This is a multicenter, randomized, controlled phase II Study of evaluating the efficacy and safety of immunotherapy combined with probiotics compound (Biolosion) in patients with advanced urothelial carcinoma.
Detailed description
This multicenter, randomized phase II trial is designed to study the efficacy and safety of probiotics compound (Biolosion) Immunotherapy of the physician's choice (IPC) plus versus IPC in patients with advanced urothelial carcinoma (aUC). Pervious received platinum-based therapies, previous received Immune checkpoint inhibitors, and the treatment lines will stratify randomization.
Interventions
DRUGProbiotics Compound (Biolosion)
15g, PO, qd
DRUGNab-paclitaxel
230mg/m2, IV, days 1, 8, q3w
DRUGCisplatin
70mg/m2, IV, days 1-3, q3w
DRUGGemcitabine
1.2g/m2, IV, days 1, 8, q3w
DRUGDisitamab vedotin
2.5mg/kg, IV, q2w
DRUGEnfortumab Vedotin
1.25mg/kg, IV, days 1, 8, q3w
DRUGPembrolizumab
200mg, IV, q3w
DRUGToripalimab
240mg, IV, q3w
Sponsors
Sun Yat-sen 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
* Patients included in this study must meet all of the following criteria: 1. Aged 18 or above; 2. Histologically or cytologically confirmed locally advanced inoperable (such as T4b, or N2-3) or metastatic urothelial carcinoma, including bladder, ureter, renal pelvis and urethra; 3. Patients who have received previous treatment with immune checkpoint inhibitors (PD-1/PD-L1 monoclonal antibodies) are allowed; 4. According to RECIST1.1 standard, there is at least one measurable target lesion; 5. ECOG score ≤2; 6. Good bone marrow, kidney (serum creatinine clearance calculated by CG formula\> 30 mL/min), liver and coagulation function: 7. Expected survival period ≥ 6 months; 8. The patient understands the research procedures and signs the informed consent form in writing to indicate his/her agreement to participate in the study; 9. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 7 days before the first dose of study drug (Cycle 1, Day 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. 10. If there is a risk of pregnancy, male and female patients should use highly effective contraception (i.e., a method with a failure rate of less than 1% per year) and continue for at least 180 days after stopping the trial treatment.
Exclusion criteria
* Any of the following will be considered as meeting the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Within approximately 48 months | Progression-Free Survival (PFS) is defined as the time from randomization to the first documented disease progression, as determined by RECIST v1.1, or death from any cause, whichever occurs first. Disease progression will be assessed by independent radiologic review. Patients without documented progression or death at the time of analysis will be censored at their last tumor assessment date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Within approximately 48 months | Overall Survival (OS) is defined as the time from randomization to death from any cause. Participants still alive at the time of analysis will be censored at the date of the last follow-up. |
| Objective Response Rate (ORR) | Within approximately 48 months | Objective Response Rate (ORR) is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as determined by RECIST v1.1 criteria, based on radiologic assessment. Responses will be confirmed by at least one subsequent imaging assessment. |
| Disease Control Rate (DCR) | Within approximately 48 months | Disease Control Rate (DCR) is defined as the proportion of participants achieving a complete response (CR), partial response (PR), or stable disease (SD) for at least 6 weeks after treatment initiation, based on RECIST v1.1 criteria. |
| Duration of Response (DOR) | Within approximately 48 months | Duration of Response (DOR) is defined as the time from the first documented objective response (CR or PR) to disease progression or death, whichever occurs first, based on RECIST v1.1 criteria. |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Within approximately 48 months | The number of participants who experience treatment-related adverse events (AEs) will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. AEs will be graded on a scale from Grade 1 (mild) to Grade 5 (death related to AE). The severity, frequency, and type of AEs will be recorded and summarized. The results will be presented as the total number and percentage of participants experiencing any treatment-related AE, as well as a breakdown by AE grade and type. Treatment-related AEs will be determined by the investigator's clinical judgment based on available data. |
| Time to Response (TTR) | Within approximately 48 months | Time to Response (TTR) is defined as the time from randomization to the first occurrence of a confirmed objective response (CR or PR) as determined by RECIST v1.1 criteria. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Analysis of the microbiota | Baseline, through study completion, an average of 48 months | The stool samples of participants before and after treatment were collected and analyzed by 16S rRNA and were used to investigate the changes in the diversity of microbiota. |
Countries
China
Contacts
Primary ContactYanxia Shi, Doctor
Backup ContactHaifeng Li, Doctor
Outcome results
None listed