Probiotics in Advanced Urothelial Carcinoma

Phase 2

Recruiting

• Conditions: Probiotics; Advanced Urothelial Carcinoma; Immunotherapy
• Interventions: Drug: Probiotics Compound (Biolosion); Drug: Cisplatin; Drug: Nab-paclitaxel; Drug: Disitamab vedotin; Drug: Gemcitabine; Drug: Enfortumab Vedotin; Drug: Pembrolizumab; Drug: Toripalimab

• Registration Number: NCT06904573
• Lead Sponsor: Sun Yat-sen University

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.

Study Timeline

• Study Start: 2025-01-01
• Status Verified: 2025-03
• Study First Submitted: 2025-03-15
• Study First Submitted QC: 2025-03-28
• Last Update Submitted: 2025-03-28
• Study First Posted: 2025-04-01
• Last Update Posted: 2025-04-01
• Primary Completion: 2027-01-01
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 222

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 exclusion criteria of the study:

  1. Patients with locally advanced disease may receive local radical treatment;
  2. History of clinically symptomatic cardiovascular, liver, respiratory, renal, hematoendocrine, or neuropsychiatric diseases;
  3. Clear brain/meningeal metastasis;
  4. Peripheral neuropathy >1 degree;
  5. Patients who have received anti-tumor monoclonal antibody treatment within 4 weeks before the start of the study, or have received other anti-tumor drug treatment and have not recovered from adverse events/reactions;
  6. Participated in any investigational drug treatment within 4 weeks before the start of treatment;
  7. Patients who had received axial bone radiotherapy within 4 weeks before the start of the study or had not recovered from adverse reactions caused by previous radiotherapy;
  8. Known severe allergic reaction to the study drug, its active ingredients and/or any excipients;
  9. Patients diagnosed with immunodeficiency or receiving systemic glucocorticoids or any other form of immunosuppressive therapy within 7 days before the first dose of the study; physiological doses of glucocorticoids (≤10 mg/day of prednisone or equivalent drugs) are allowed;
  10. Active autoimmune diseases requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) occurred within 2 years before the first dose. Replacement therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatment; a history of non-infectious pneumonia requiring glucocorticoid treatment within 1 year before the first dose or current interstitial lung disease;
  11. Received solid organ or blood system transplantation;
  12. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive). Untreated active hepatitis B;
  13. Untreated active hepatitis B; Note: Hepatitis B subjects who meet the following criteria are also eligible for inclusion: HBV viral load must be <1000 copies/ml (200 IU/ml) before the first dose, and subjects should receive anti-HBV treatment during the entire study chemotherapy treatment to avoid viral reactivation. For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), preventive anti-HBV treatment is not required, but viral reactivation needs to be closely monitored;
  14. Subjects with active HCV infection (HCV antibody positive and HCV-RNA level above the detection limit) received live vaccine within 30 days before the first dose (Cycle 1, Day 1);
  15. A history of other malignant tumors in the past 5 years, excluding cured non-malignant melanoma of the skin, cervical carcinoma in situ, and incidentally discovered prostate cancer (stage lower than T2N0M0, Gleason score <7, or undetectable PSA);
  16. Medical history or disease evidence, abnormal treatment or laboratory test values, or other conditions that the researcher considers unsuitable for enrollment that may interfere with the trial results or prevent the subject from fully participating in the study;
  17. Breastfeeding women
  18. People with chronic diseases who need to take antibiotics for a long time.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experiment group	Probiotics Compound (Biolosion)	Subjects in this arm will receive an oral probiotics compound (Biolosion) plus the Investigator's choice of immune checkpoint inhibitor-based (ICIs-based) therapies: Regimens that combine with chemotherapy agents can include but are not limited to Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin, Enfortumab Vedotin; Immune checkpoint inhibitors include but are not limited to Pembrolizumab and toripalimab.
Experiment group	Toripalimab	Subjects in this arm will receive an oral probiotics compound (Biolosion) plus the Investigator's choice of immune checkpoint inhibitor-based (ICIs-based) therapies: Regimens that combine with chemotherapy agents can include but are not limited to Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin, Enfortumab Vedotin; Immune checkpoint inhibitors include but are not limited to Pembrolizumab and toripalimab.
Control group	Cisplatin	Subjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies
Experiment group	Nab-paclitaxel	Subjects in this arm will receive an oral probiotics compound (Biolosion) plus the Investigator's choice of immune checkpoint inhibitor-based (ICIs-based) therapies: Regimens that combine with chemotherapy agents can include but are not limited to Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin, Enfortumab Vedotin; Immune checkpoint inhibitors include but are not limited to Pembrolizumab and toripalimab.
Experiment group	Pembrolizumab	Subjects in this arm will receive an oral probiotics compound (Biolosion) plus the Investigator's choice of immune checkpoint inhibitor-based (ICIs-based) therapies: Regimens that combine with chemotherapy agents can include but are not limited to Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin, Enfortumab Vedotin; Immune checkpoint inhibitors include but are not limited to Pembrolizumab and toripalimab.
Experiment group	Cisplatin	Subjects in this arm will receive an oral probiotics compound (Biolosion) plus the Investigator's choice of immune checkpoint inhibitor-based (ICIs-based) therapies: Regimens that combine with chemotherapy agents can include but are not limited to Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin, Enfortumab Vedotin; Immune checkpoint inhibitors include but are not limited to Pembrolizumab and toripalimab.
Control group	Disitamab vedotin	Subjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies
Control group	Enfortumab Vedotin	Subjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies
Experiment group	Gemcitabine	Subjects in this arm will receive an oral probiotics compound (Biolosion) plus the Investigator's choice of immune checkpoint inhibitor-based (ICIs-based) therapies: Regimens that combine with chemotherapy agents can include but are not limited to Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin, Enfortumab Vedotin; Immune checkpoint inhibitors include but are not limited to Pembrolizumab and toripalimab.
Experiment group	Disitamab vedotin	Subjects in this arm will receive an oral probiotics compound (Biolosion) plus the Investigator's choice of immune checkpoint inhibitor-based (ICIs-based) therapies: Regimens that combine with chemotherapy agents can include but are not limited to Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin, Enfortumab Vedotin; Immune checkpoint inhibitors include but are not limited to Pembrolizumab and toripalimab.
Experiment group	Enfortumab Vedotin	Subjects in this arm will receive an oral probiotics compound (Biolosion) plus the Investigator's choice of immune checkpoint inhibitor-based (ICIs-based) therapies: Regimens that combine with chemotherapy agents can include but are not limited to Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin, Enfortumab Vedotin; Immune checkpoint inhibitors include but are not limited to Pembrolizumab and toripalimab.
Control group	Nab-paclitaxel	Subjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies
Control group	Gemcitabine	Subjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies
Control group	Pembrolizumab	Subjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies
Control group	Toripalimab	Subjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.

Trial Locations

Locations (3)

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology; 🇨🇳 Wuhan, Hubei, China

Sun yat-sen university cancer center; 🇨🇳 Guangzhou, Guangdong, China

Sun Yat-sen Memorial Hospital; 🇨🇳 Guangzhou, Guangdong, China