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Probiotics Combined With Targeted Therapy Plus Immunotherapy in Bladder-Preserving Setting for Patients With MIBC

ConditionMuscle Invasive Bladder Cancer (MIBC)
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
Sponsorchenxu

About this trial

The goal of this clinical trial is to learn if oral probiotics (Clostridium butyricum) work to improve the efficacy of targeted therapy plus immunotherapy in bladder preservation setting for cisplatin-ineligible T2-3N0M0 bladder cancer patients with low serum butyrate.

The main questions it aims to answer are: Do oral probiotics elevate serum butyrate levels and enhance the duation of bladder preservation interval with targeted therapy plus immunotherapy? Researchers will compare oral probiotics combined with targeted therapy plus immunotherapy to standard regimens (targeted therapy plus immunotherapy) to see if oral probiotics can improve its efficacy.

Participants will:

1. Take oral probiotics and/or Disitamab Vedotin (HER2-ADC) and Toripalimab (PD-L1 inhibitor) for one year in total, which is divided into induction treatment period, intensive treatment period and maintenance treatment period. 2. Return to the hospital for evaluation of tumor residual burden according to the follow-up plan, which will include urine cytology, imaging, surgical biopsy, and urine DNA methylation detection.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients have histologically confirmed, radiologically staged cT2-3N0M0 urothelial carcinoma of the bladder, in which urothelial carcinoma is the predominant component (>50%).

Serum butyrate level <46 μg/L as determined by quantitative mass spectrometry.

HER2 expression is assessed by immunohistochemistry (IHC) on pretreatment tumor specimens, with confirmed IHC ≥1+.

Patients are deemed ineligible for radical cystectomy based on laboratory evaluation and patient preference.

Disqualifiers

Prior ADCs or PD-1/PD-L1 inhibitor therapy.

Known hypersensitivity to microbiota-related preparations (microecological products), RC48-ADC or Toripalimab or any of its components.

Receipt of other approved systemic anticancer therapy or systemic immunomodulatory agents (including but not limited to interferon, interleukin-2, and tumour necrosis factor) within 28 days prior to enrolment.

Prior radiotherapy for bladder cancer.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Probiotic

    Drug

    80 mg orally twice daily during induction and intensive treatment periods; 80 mg orally twice daily, 3 weeks on / 3 weeks off dosing schedule during maintenance treatment period

  • Disitamab Vedotin

    Drug

    2.0 mg/kg IV every 2 weeks during the induction treatment period and intensive treatment period

  • Toripalimab

    Drug

    3.0 mg/kg IV every 2 weeks during the induction and intensive treatment periods; followed by 240 mg IV every 3 weeks during the maintenance treatment period.

Treatment groups

146 Participants
are divided into 2 treatment groups
Group A: Probiotic + Disitamab Vedotin + ToripalimabExperimental treatment 3 interventions
Group B: Disitamab Vedotin + ToripalimabActive comparator 2 interventions

Trial outcomes

Primary outcomes

1

bladder-intact event free survival (BI-EFS), evaluated by independent review committee

Bladder intact event-free survival (BIEFS) refers to the time from the date of randomization to the first occurrence of any bladder preservation failure event through tumor control, whichever occurs first. Bladder preservation failure events include: 1. Rapid progression: progressive disease (PD) assessed by imaging at the mid-induction evaluation; 2. Tumor recurrence: ≥T2 stage, high-grade urothelial carcinoma (per the WHO 2016 Classification of Tumours of the Urinary System), or non-urothelial carcinoma histology; 3. Tumor metastasis: including lymph node metastasis and distant organ metastasis; 4. Death from any cause; 5. Receipt of radical cystectomy for any other reason.

Time frame
Up to approximately 3 years

Secondary outcomes

1

clinical complete response (cCR)

Clinical complete response rate (cCR) refers to the proportion of participants who achieve all of the following criteria after completion of induction treatment: first, negative urine cytology; second, no new lymph node metastasis or distant metastatic lesions identified on imaging examinations; third, no malignant tumor identified on cystoscopy biopsy, or only low-grade Ta/T1 urothelial carcinoma present.

Time frame
Up to approximately 3 years
2

Metastasis-free survival (MFS)

Metastasis-free survival (MFS) refers to the time from the date of randomization to the first occurrence of lymph node metastasis or distant organ metastasis, whichever occurs first.

Time frame
Up to approximately 3 years
3

Overall survival (OS)

Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject.

Time frame
Up to approximately 3 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

chenxu

Lead sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Sponsor institution

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: