A Multicenter Randomized Controlled Study to Evaluate the Efficacy of Oral Probiotics Combined With PD-1 Monoclonal Antibody and Disitamab Vedotin in Bladder-Preserving Setting for Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer and Low Serum Butyrate
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 146
- 试验地点
- 1
- 主要终点
- bladder-intact event free survival (BI-EFS), evaluated by independent review committee
研究概览
简要总结
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:
- 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.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Patients considered ineligible for cisplatin therapy and meeting at least one of the following criteria: ECOG performance status >1 or Karnofsky performance status of 60-70%; Creatinine clearance <60 mL/min; Hearing loss ≥ Grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0; Peripheral neuropathy ≥ Grade 2 (NCI-CTCAE v5.0); New York Heart Association (NYHA) Class III or higher heart failure.
- •ECOG performance status of 0-
- •Adequate cardiac, bone marrow, hepatic, renal, and coagulation functions.
排除标准
- •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.
- •Prior antitumour drug therapy, except for the following: a. For patients who previously received systemic chemotherapy, a treatment-free interval of at least 3 months between the last dose and the start of induction therapy is required; b. Local intravesical chemotherapy or immunotherapy (including BCG) must be completed at least 1 week before initiation of study neoadjuvant treatment.
- •Surgery or significant trauma within 28 days prior to enrolment (implantation of vascular access devices and TURBT are not considered).
- •Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to enrolment.
- •Receipt of live vaccines within 28 days prior to enrolment.
- •Active autoimmune disease requiring systemic treatment and considered by the investigator to potentially interfere with the study treatment.
- •Requirement for long-term high-dose corticosteroids or other immunosuppressive agents.
- •Clinically significant abnormalities that may affect treatment, including electrolyte disturbances, hypoalbuminaemia, interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases. These include uncontrolled diabetes, hypertension, or cardiovascular disease, such as active cardiac conditions within 6 months prior to enrolment.
- •Untreated chronic hepatitis B with HBV DNA ≥500 IU/mL (2,500 copies/mL) or known HBV carriers with active disease.
- •Active hepatitis C infection.
- •History of immunodeficiency, including positive human immunodeficiency virus (HIV) test, other acquired or congenital immunodeficiency disorders, or a history of allogeneic stem cell transplantation or solid organ transplantation.
- •Toxicities from prior therapies that have not recovered to baseline or stabilised.
- •Presence of other concomitant malignancies.
研究组 & 干预措施
Probiotic + Disitamab Vedotin + Toripalimab
Participants will receive oral Clostridium butyricum viable tablets, disitamab vedotin, and toripalimab for about 1 year, or until investigator-assessed bladder preservation failure, loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Probiotic (Drug)
Probiotic + Disitamab Vedotin + Toripalimab
Participants will receive oral Clostridium butyricum viable tablets, disitamab vedotin, and toripalimab for about 1 year, or until investigator-assessed bladder preservation failure, loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Disitamab Vedotin (Drug)
Probiotic + Disitamab Vedotin + Toripalimab
Participants will receive oral Clostridium butyricum viable tablets, disitamab vedotin, and toripalimab for about 1 year, or until investigator-assessed bladder preservation failure, loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
Disitamab Vedotin + Toripalimab
Participants will receive disitamab vedotin and toripalimab for about 1 year, or until investigator-assessed bladder preservation failure, loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Disitamab Vedotin (Drug)
Disitamab Vedotin + Toripalimab
Participants will receive disitamab vedotin and toripalimab for about 1 year, or until investigator-assessed bladder preservation failure, loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
结局指标
主要结局
bladder-intact event free survival (BI-EFS), evaluated by independent review committee
时间窗: Up to approximately 3 years
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.
次要结局
- clinical complete response (cCR)(Up to approximately 3 years)
- Metastasis-free survival (MFS)(Up to approximately 3 years)
- Overall survival (OS)(Up to approximately 3 years)
研究者
chenxu
PhD, MD
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University