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Advanced Urothelial CarcinomaPhase 2IMPROVENCT06904573

Probiotics in Advanced Urothelial Carcinoma

A Phase 2 study testing Probiotics Compound (Biolosion), Nab-paclitaxel and Cisplatin in people with Advanced Urothelial Carcinoma and Probiotics, run by Sun Yat-sen University at 3 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Probiotics Compound (Biolosion), Nab-paclitaxel and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
222 participants
Where
3 sitesChina
Study dates
1 Jan 2025to 1 Jan 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients included in this study must meet all of the following criteria:
  • Aged 18 or above;
  • Histologically or cytologically confirmed locally advanced inoperable (such as T4b, or N2-3) or metastatic urothelial carcinoma, including bladder, ureter, renal pelvis and urethra;
  • Patients who have received previous treatment with immune checkpoint inhibitors (PD-1/PD-L1 monoclonal antibodies) are allowed;
  • According to RECIST1.1 standard, there is at least one measurable target lesion;
  • ECOG score ≤2;
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  • Good bone marrow, kidney (serum creatinine clearance calculated by CG formula> 30 mL/min), liver and coagulation function:
  • Expected survival period ≥ 6 months;
  • The patient understands the research procedures and signs the informed consent form in writing to indicate his/her agreement to participate in the study;
  • 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.
  • 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.

Who cannot join

  • Any of the following will be considered as meeting the exclusion criteria of the study:
  • Patients with locally advanced disease may receive local radical treatment;
  • History of clinically symptomatic cardiovascular, liver, respiratory, renal, hematoendocrine, or neuropsychiatric diseases;
  • Clear brain/meningeal metastasis;
  • Peripheral neuropathy >1 degree;
  • 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;
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  • Participated in any investigational drug treatment within 4 weeks before the start of treatment;
  • 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;
  • Known severe allergic reaction to the study drug, its active ingredients and/or any excipients;
  • 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;
  • 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;
  • Received solid organ or blood system transplantation;
  • Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive). Untreated active hepatitis B;
  • 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;
  • 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);
  • 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);
  • 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;
  • Breastfeeding women
  • People with chronic diseases who need to take antibiotics for a long time.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Yanxia Shi, Doctor contact

86-020-87343486

shiyx@sysucc.org.cn

Haifeng Li, Doctor contact

86-020-87343486

lihf@sysucc.org.cn

China3 sites, 3 recruiting

  • Sun yat-sen university cancer center

    Guangzhou, Guangdong, 510000

    Yanxia Shi, Doctor, 86-020-87343486, shiyx@sysucc.org.cn

    Recruiting

  • Sun Yat-sen Memorial Hospital

    Guangzhou, Guangdong

    Tao QIn, Doctor

    Not yet recruiting

  • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

    Wuhan, Hubei

    Bo Liu, Doctor

    Not yet recruiting

Other trials in China

About this study

Official title: 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.

Read the 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.

Being tested
Probiotics Compound (Biolosion), Nab-paclitaxel, Cisplatin, Gemcitabine, Disitamab vedotin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Probiotics Compound (Biolosion)Drug

    15g, PO, qd

  • Nab-paclitaxelDrug

    230mg/m2, IV, days 1, 8, q3w

  • CisplatinDrug

    70mg/m2, IV, days 1-3, q3w

  • GemcitabineDrug

    1.2g/m2, IV, days 1, 8, q3w

  • Disitamab vedotinDrug

    2.5mg/kg, IV, q2w

  • Enfortumab VedotinDrug

    1.25mg/kg, IV, days 1, 8, q3w

  • PembrolizumabDrug

    200mg, IV, q3w

  • ToripalimabDrug

    240mg, IV, q3w

Study groups in NCT06904573
Study groupRoleWhat they receive
Experiment groupExperimentalSubjects 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.
Receives: Drug: Probiotics Compound (Biolosion); Drug: Nab-paclitaxel; Drug: Cisplatin; Drug: Gemcitabine; Drug: Disitamab vedotin; Drug: Enfortumab Vedotin; Drug: Pembrolizumab; Drug: Toripalimab
Control groupActive comparatorSubjects in this arm will receive Investigator's choice of immune checkpoint inhibitors-based (ICIs-based) therapies
Receives: Drug: Nab-paclitaxel; Drug: Cisplatin; Drug: Gemcitabine; Drug: Disitamab vedotin; Drug: Enfortumab Vedotin; Drug: Pembrolizumab; Drug: Toripalimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    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.

    Measured: Within approximately 48 months

Secondary outcomes (6)

  1. Overall Survival (OS)

    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.

    Measured: Within approximately 48 months

  2. Objective Response Rate (ORR)

    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.

    Measured: Within approximately 48 months

  3. Disease Control Rate (DCR)

    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.

    Measured: Within approximately 48 months

  4. Time to Response (TTR)

    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.

    Measured: Within approximately 48 months

  5. Duration of Response (DOR)

    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.

    Measured: Within approximately 48 months

  6. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    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.

    Measured: Within approximately 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2025
  2. Study start1 Jan 2025
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
222 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06904573
Sponsor's protocol ID
2024-FXY-297
Acronym
IMPROVE
Status last verified
Mar 2025
First submitted
15 Mar 2025
Last updated
1 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual participant data (IPD) will not be shared due to ethical and privacy concerns.

Publications

  • Dizman N, Meza L, Bergerot P, Alcantara M, Dorff T, Lyou Y, Frankel P, Cui Y, Mira V, Llamas M, Hsu J, Zengin Z, Salgia N, Salgia S, Malhotra J, Chawla N, Chehrazi-Raffle A, Muddasani R, Gillece J, Reining L, Trent J, Takahashi M, Oka K, Higashi S, Kortylewski M, Highlander SK, Pal SK. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med. 2022 Apr;28(4):704-712. doi: 10.1038/s41591-022-01694-6. Epub 2022 Feb 28.

    PubMed 35228755

  • Miyake M, Oda Y, Owari T, Iida K, Ohnishi S, Fujii T, Nishimura N, Miyamoto T, Shimizu T, Ohnishi K, Hori S, Morizawa Y, Gotoh D, Nakai Y, Torimoto K, Tanaka N, Fujimoto K. Probiotics enhances anti-tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer. Cancer Sci. 2023 Mar;114(3):1118-1130. doi: 10.1111/cas.15666. Epub 2022 Nov 30.

    PubMed 36398663

  • Messaoudene M, Pidgeon R, Richard C, Ponce M, Diop K, Benlaifaoui M, Nolin-Lapalme A, Cauchois F, Malo J, Belkaid W, Isnard S, Fradet Y, Dridi L, Velin D, Oster P, Raoult D, Ghiringhelli F, Boidot R, Chevrier S, Kysela DT, Brun YV, Falcone EL, Pilon G, Onate FP, Gitton-Quent O, Le Chatelier E, Durand S, Kroemer G, Elkrief A, Marette A, Castagner B, Routy B. A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti-PD-1 Resistance through Effects on the Gut Microbiota. Cancer Discov. 2022 Apr 1;12(4):1070-1087. doi: 10.1158/2159-8290.CD-21-0808.

    PubMed 35031549

  • Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084-9. doi: 10.1126/science.aac4255. Epub 2015 Nov 5.

    PubMed 26541606

  • Li WT, Iyangar AS, Reddy R, Chakladar J, Bhargava V, Sakamoto K, Ongkeko WM, Rajasekaran M. The Bladder Microbiome Is Associated with Epithelial-Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma. Cancers (Basel). 2021 Jul 21;13(15):3649. doi: 10.3390/cancers13153649.

    PubMed 34359550

  • Grande E, G.M., Arranz Arija JA, et al., IMvigor130: a phase III study of atezolizumab with or without platinum-based chemotherapy in previously untreated metastatic urothelial carcinoma. Presented at: . ESMO Congress; , 2019 Abstract LBA14.

  • Lichtenegger FS, Rothe M, Schnorfeil FM, Deiser K, Krupka C, Augsberger C, Schluter M, Neitz J, Subklewe M. Targeting LAG-3 and PD-1 to Enhance T Cell Activation by Antigen-Presenting Cells. Front Immunol. 2018 Feb 27;9:385. doi: 10.3389/fimmu.2018.00385. eCollection 2018.

    PubMed 29535740

  • Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, Chaput N, Eggermont A, Marabelle A, Soria JC, Ferte C. Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1. Clin Cancer Res. 2017 Apr 15;23(8):1920-1928. doi: 10.1158/1078-0432.CCR-16-1741. Epub 2016 Nov 8.

    PubMed 27827313

  • Vaughn DJ, Bellmunt J, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Li H, Perini RF, Bajorin DF, de Wit R. Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial Cancer. J Clin Oncol. 2018 Jun 1;36(16):1579-1587. doi: 10.1200/JCO.2017.76.9562. Epub 2018 Mar 28.

    PubMed 29590008

  • Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411. doi: 10.1001/jamaoncol.2017.2411. Epub 2017 Sep 14.

    PubMed 28817753

  • Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, Plimack ER, Vaena D, Grimm MO, Bracarda S, Arranz JA, Pal S, Ohyama C, Saci A, Qu X, Lambert A, Krishnan S, Azrilevich A, Galsky MD. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):312-322. doi: 10.1016/S1470-2045(17)30065-7. Epub 2017 Jan 26.

    PubMed 28131785

  • Petrylak DP, Powles T, Bellmunt J, Braiteh F, Loriot Y, Morales-Barrera R, Burris HA, Kim JW, Ding B, Kaiser C, Fasso M, O'Hear C, Vogelzang NJ. Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. JAMA Oncol. 2018 Apr 1;4(4):537-544. doi: 10.1001/jamaoncol.2017.5440.

    PubMed 29423515

  • Sio TT, Ko J, Gudena VK, Verma N, Chaudhary UB. Chemotherapeutic and targeted biological agents for metastatic bladder cancer: a comprehensive review. Int J Urol. 2014 Jul;21(7):630-7. doi: 10.1111/iju.12407. Epub 2014 Jan 23.

    PubMed 24455982

  • Lin CC, Hsu CH, Huang CY, Keng HY, Tsai YC, Huang KH, Cheng AL, Pu YS. Gemcitabine and ifosfamide as a second-line treatment for cisplatin-refractory metastatic urothelial carcinoma: a phase II study. Anticancer Drugs. 2007 Apr;18(4):487-91. doi: 10.1097/CAD.0b013e3280126603.

    PubMed 17351402

  • Sweeney CJ, Roth BJ, Kabbinavar FF, Vaughn DJ, Arning M, Curiel RE, Obasaju CK, Wang Y, Nicol SJ, Kaufman DS. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006 Jul 20;24(21):3451-7. doi: 10.1200/JCO.2005.03.6699.

    PubMed 16849761

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Probiotics Compound (Biolosion), Nab-paclitaxel and Cisplatin in people with Advanced Urothelial Carcinoma and Probiotics, run by Sun Yat-sen University at 3 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yanxia Shi, Doctor (86-020-87343486, shiyx@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: Within approximately 48 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06904573, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2025.

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