Probiotics in Advanced Urothelial Carcinoma (IMPROVE)

March 28, 2025 updated by: Shi Yanxia, Sun Yat-sen University

A Multicenter, Randomized Controlled Phase II Study of Evaluating the Efficacy and Safety of Immunotherapy Combined With Oral Probiotics Compound (Biolosion) in Patients With Advanced Urothelial Carcinoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

222

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • Sun Yat-Sen Memorial Hospital
        • Contact:
          • Tao QIn, Doctor
    • Hubei
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
        • Contact:
          • Bo Liu, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experiment group

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.
Drug: Probiotics Compound (Biolosion)
15g, PO, qd
Drug: Nab-paclitaxel
230mg/m2, IV, days 1, 8, q3w
Drug: Cisplatin
70mg/m2, IV, days 1-3, q3w
Drug: Gemcitabine
1.2g/m2, IV, days 1, 8, q3w
Drug: Disitamab vedotin
2.5mg/kg, IV, q2w
Drug: Enfortumab Vedotin
1.25mg/kg, IV, days 1, 8, q3w
Drug: Pembrolizumab
200mg, IV, q3w
Drug: Toripalimab
240mg, IV, q3w
Active Comparator: Control group
Subjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies
Drug: Nab-paclitaxel
230mg/m2, IV, days 1, 8, q3w
Drug: Cisplatin
70mg/m2, IV, days 1-3, q3w
Drug: Gemcitabine
1.2g/m2, IV, days 1, 8, q3w
Drug: Disitamab vedotin
2.5mg/kg, IV, q2w
Drug: Enfortumab Vedotin
1.25mg/kg, IV, days 1, 8, q3w
Drug: Pembrolizumab
200mg, IV, q3w
Drug: Toripalimab
240mg, IV, q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: 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.
Within approximately 48 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 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.
Within approximately 48 months
Objective Response Rate (ORR)
Time Frame: 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.
Within approximately 48 months
Disease Control Rate (DCR)
Time Frame: 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.
Within approximately 48 months
Time to Response (TTR)
Time Frame: 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.
Within approximately 48 months
Duration of Response (DOR)
Time Frame: 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.
Within approximately 48 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 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.
Within approximately 48 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analysis of the microbiota
Time Frame: 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.
Baseline, through study completion, an average of 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Yanxia Shi, Doctor, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2025

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

March 15, 2025

First Submitted That Met QC Criteria

March 28, 2025

First Posted (Actual)

April 1, 2025

Study Record Updates

Last Update Posted (Actual)

April 1, 2025

Last Update Submitted That Met QC Criteria

March 28, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-FXY-297

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data (IPD) will not be shared due to ethical and privacy concerns.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Probiotics

Clinical Trials on Probiotics Compound (Biolosion)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Senegal

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe