Clinical Research Directory

Is Prolonged Systemic Immunotherapy Necessary After Achieving Tumor-free Status in Patients With Extensive Transurethrally Unresectable Very-high-risk NMIBC?

Patients with extensive transurethrally unresectable very-high-risk non-muscle-invasive bladder cancer (NMIBC) may achieve a tumor-free status after systemic immunotherapy-based bladder-sparing treatment combined with transurethral resection of bladder tumor (TURBT). However, the optimal duration of systemic immunotherapy after achieving a tumor-free status remains uncertain. Prolonged treatment may increase toxicity, treatment burden, and cost, while some patients may maintain durable disease control without continued therapy. This randomized study aims to evaluate whether active surveillance after achieving tumor-free status is a feasible alternative to continued systemic immunotherapy in patients with extensive transurethrally unresectable very-high-risk NMIBC. Patients will initially receive systemic immunotherapy-based treatment followed by disease evaluation using cystoscopy with biopsy and/or TURBT, urine cytology, urinary tumor DNA (utDNA), and imaging assessments. Patients who achieve tumor-free status after treatment and complete resection of visible disease will be randomized to either active surveillance or continued systemic immunotherapy. The study will evaluate recurrence outcomes, bladder preservation, progression, safety, and patient management strategies following achievement of tumor-free status. The trial also aims to explore the role of urinary tumor DNA in identifying patients who may safely undergo treatment de-escalation and active surveillance.

The Role of Definitive Radiotherapy in Non Muscle Invasive Bladder Cancer

Bladder cancer is one of the most common malignancies worldwide and represents a major global health burden. According to the GLOBOCAN 2022 estimates, approximately 614,298 new cases and 220,596 deaths from bladder cancer were reported worldwide, making it the ninth most commonly diagnosed malignancy globally. Non-muscle-invasive bladder cancer (NMIBC), comprising Ta, T1, and carcinoma in situ (CIS), accounts for approximately three-quarters of newly diagnosed bladder cancers. Although NMIBC is confined to the mucosa or submucosa, it represents a heterogeneous group of tumors with markedly different risks of recurrence and progression, with the highest risk observed in high-grade and high-risk disease. NMIBC is classified according to the risk of recurrence and progression into low-, intermediate-, high-, and very-high-risk groups. Risk stratification incorporates tumor stage, histological grade, tumor size, number of tumors, recurrence pattern, presence of CIS, age, and other adverse pathological and clinical features. High-grade histology, particularly T1 high-grade disease, is associated with a substantially increased risk of progression to muscle-invasive bladder cancer. Risk Stratification of Non-Muscle-Invasive Bladder Cancer Risk group Main clinical and pathological characteristics Low-risk Primary, solitary, small low-grade Ta tumor without CIS and without significant adverse risk factors Intermediate-risk Tumors that do not fulfill the criteria for low-, high-, or very-high-risk disease High-risk Includes high-grade T1 tumors and CIS, as well as selected high-grade Ta/T1 tumors with additional adverse risk factors Very-high-risk High-grade tumors with multiple adverse features, including selected T1 high-grade tumors associated with CIS and/or multiple additional risk factors Risk classification should follow current guideline-defined criteria and should not be based on histological grade alone. The management of high-risk NMIBC is based on complete transurethral resection of the bladder tumor (TURBT), followed by risk-adapted intravesical therapy. Full-dose intravesical Bacillus Calmette-Guérin (BCG) with maintenance therapy for one to three years remains an established standard treatment for high-risk disease, while radical cystectomy should be discussed in selected patients, particularly those with very-high-risk features. T1 high-grade disease represents a particularly challenging subgroup because of its substantial potential for recurrence and progression despite bladder-preserving treatment. Clinical series of patients treated with TURBT followed by BCG have demonstrated considerable rates of both recurrent and progressive disease, emphasizing the need for effective treatment strategies in patients at high risk of treatment failure. Radiotherapy has historically had a limited role in NMIBC. Nevertheless, its biological activity against urothelial carcinoma and its established role in bladder-preserving treatment of selected muscle-invasive bladder cancer have provided a rationale for investigating radiotherapy at earlier stages of bladder cancer. Modern radiotherapy techniques may allow treatment of the bladder while limiting radiation exposure to surrounding normal tissues. Clinical evidence for radiotherapy in high-risk NMIBC has been reported since the early 1980s. Retrospective series evaluating radiotherapy in high-risk T1 bladder cancer demonstrated clinically meaningful complete response rates, local control, long-term survival, and bladder preservation. These findings suggest that radiotherapy may represent a potential bladder-preserving treatment option in carefully selected patients. A systematic review and meta-analysis evaluating radiotherapy for high-risk NMIBC identified 13 studies involving 746 patients. The reported five-year recurrence-free survival, cancer-specific survival, and overall survival were 54%, 86%, and 72%, respectively. Approximately 13% of patients subsequently underwent salvage radical cystectomy and 9% developed metastatic disease. However, the available evidence was considered low quality because most studies were retrospective and heterogeneous, emphasizing the need for prospective clinical evaluation. The potential role of radiotherapy in BCG-naïve high-risk NMIBC is of clinical interest because it could provide a bladder-preserving local treatment approach without prolonged intravesical therapy in selected patients. However, current guidelines do not consider radiotherapy a standard replacement for BCG-naïve high-risk NMIBC, and prospective evidence remains limited. Therefore, there is a need for prospective evaluation of radiotherapy as a bladder-preserving treatment strategy in selected patients with high-risk NMIBC, who present without previous BCG exposure, and Evaluation of local disease control, bladder preservation, progression, survival, and treatment-related toxicity may help clarify the potential role of RTH

A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer

This is a first-in-human, multicenter, Phase 1/1b, 3-part, double-blind study of ZH9 in patients with recurrent NMIBC who are eligible for intravesical therapy. In Part 1, the safety, tolerability, and pharmacology of ZH9 IVI will be evaluated in a single ascending dose (SAD) patient cohort. In Part 2, the safety, tolerability, and pharmacology of ZH9 oral prime followed by ZH9 IVI will be evaluated in 2 patient cohorts at the doses and schedule established in Part 1. In Part 3, the safety, pharmacology, and clinical efficacy of ZH9 will be further evaluated in 2 expansion cohorts of patients with recurrent intermediate- and high-risk NMIBC.

Toripalimab Combined With Intravesical Gemcitabine as Adjuvant Therapy for High-Risk Non-Muscle-Invasive Bladder Cancer After TURBT

This is a prospective, open-label, single-center, single-arm phase II clinical study to evaluate the efficacy and safety of toripalimab combined with intravesical gemcitabine as adjuvant therapy in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Patients with high-risk NMIBC are planned to be enrolled. Treatment consists of one immediate intravesical instillation of gemcitabine after TURBT, followed by induction intravesical chemotherapy with gemcitabine for 4-8 instillations, and then maintenance treatment with toripalimab combined with intravesical gemcitabine 2000 mg once monthly for 12 instillations.

A Study to Evaluate the Safety and Efficacy of NDV-01 in Participants With NMIBC

This is a prospective, single-arm study evaluating the safety and efficacy of NDV01 KIT, a fixed-dose combination of gemcitabine HCl and docetaxel, administered via intravesical instillation in patients with high-grade Non-Muscle Invasive Bladder Cancer (NMIBC). NDV01 KIT includes 60 mL Carbopol Gel followed by 15 g NDV01 solution (gemcitabine HCl 1000 mg and docetaxel 40 mg), administered biweekly for six treatments, followed by monthly maintenance therapy for up to 12 months. The study includes a pharmacokinetic (PK) sub-study assessing systemic exposure to NDV01's active ingredients.

Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin

This is a Phase 3, open-label, single arm trial designed to evaluate Cretostimogene patients with NMIBC who have failed prior BCG therapy. Up to approximately 115 CIS bladder cancer patients with or without HG Ta or HG T1 papillary disease will be enrolled under the original protocol through Amendment 4, which will comprise Cohort C. Cohort C is closed to enrollment. Under Amendment 5-1, Cohort P was added to enroll up to 70 patients with HG Ta/T1 papillary bladder cancer. Under Amendment 6, the target number of patients enrolled in Cohort P was increased to 75. Cohort P is open to enrollment Cohort C and Cohort P will be analyzed and reported separately. Patients will have had to fail prior BCG therapy which is defined as having persistent or recurrent disease within 12 months (Cohort C) or 6 months (Cohort P) following the completion of adequate BCG therapy for HGUC

A Study of Adjuvant Cretostimogene Grenadenorepvec for Treatment of Intermediate Risk NMIBC Following TURBT

This is a Phase 3, open-label, randomized trial designed to evaluate the RFS of TURBT followed by cretostimogene grenadenorepvec versus TURBT followed by surveillance for the treatment of participants with IR-NMIBC.

Intravesical Chemotherapy in Combination With Systemic Pembrolizumab in NMIBC Unresponsive or Exposed to BCG Therapy

interventional study of intravesical chemotherapy and sistemic immunotherapy in NMIBC

Comparison of CT and MR (VI-RADS) Imaging for Local Bladder Cancer Staging

This prospective diagnostic accuracy study compares computed tomography (CT) and multiparametric magnetic resonance imaging (MRI) using the Vesical Imaging-Reporting and Data System (VI-RADS) for local staging of newly diagnosed bladder cancer. All participants undergo both imaging modalities prior to transurethral resection of the bladder tumor (TURBT) or cystectomy. Histopathology serves as the reference standard.

Hyperthermic Intravesical Chemotherapy (HIVEC) in BCG-Non-Responsive High-Grade NMIBC Patients

This is a Phase II, prospective, single-arm, open-label clinical study evaluating hyperthermic intravesical chemotherapy (HIVEC) with Mitomycin C in patients with high-grade, non-muscle-invasive bladder cancer (NMIBC) who are BCG-non-responsive or BCG-intolerant and are ineligible for, or refuse, radical cystectomy. Mitomycin C is an approved medicinal product used within routine clinical practice and administered with a CE-marked recirculation device (BRS Combat system) that maintains the solution at approximately 43°C for 60 minutes. The treatment schedule consists of 6 weekly induction instillations followed by 9 monthly maintenance instillations. The co-primary objectives are to describe the safety and toxicity profile of HIVEC, including treatment discontinuations due to procedure-related toxicity, and to estimate the 12-month recurrence-free survival (12moRFS). Secondary objectives include characterizing patterns of non-muscle-invasive and muscle-invasive recurrences, bladder cancer-specific survival, overall survival, and quality of life. Approximately 50 patients will be enrolled in this single-center pilot study to generate exploratory safety and efficacy data in this high-risk population and to support the design of future randomized trials

Follow up of Intravesical N-803 Plus BCG in BCG-Naive Non-Muscle Invasive Bladder Cancer (NMIBC)

The purpose of this clinical trial is to obtain long-term follow-up information and status of bladder cancer for patients who received study treatment in the QUILT-2.005 study.

Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin

This study aims to evaluate the efficacy and safety of Cretostimogene in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without Ta/T1 papillary tumors.

Efficacy of Gemcitabine Submucosal Injection for Preventing Recurrence in Intermediate- and High-Risk Non-Muscle-Invasive Bladder Cancer: A Randomized Trial

Bladder cancer is the most common malignant tumor of the urinary system in China, and its incidence has been increasing year by year. It is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). NMIBC accounts for 75% of newly diagnosed bladder cancer cases, and transurethral resection of bladder tumor (TURBT) followed by postoperative intravesical therapy is the standard treatment for NMIBC. However, the 5-year recurrence rate of NMIBC remains as high as 50%, with 20-30% of patients progressing to MIBC. MIBC is characterized by rapid progression and a high tendency for metastasis. The 5-year survival rate for patients with metastatic bladder cancer is only 5.4%. This study aims to investigate the efficacy of submucosal injection of the chemotherapeutic agent gemcitabine in preventing recurrence of intermediate- and high-risk NMIBC. Additionally, it seeks to develop software and devices related to submucosal injection to promote the clinical application of this new approach in the chemotherapeutic management of NMIBC. This research is expected to bring a revolutionary breakthrough in the standardisation of whole-process diagnosis and treatment of NMIBC, holding significant scientific value and major clinical translational importance for improving therapeutic outcomes and prognosis of bladder cancer.

A Study Comparing the Necessity of a Second Transurethral Resection in High-Risk Non-Muscle-Invasive Bladder Cancer Patients With Negative Results From Post-Initial Resection Urine Genome-Wide Low-Depth Sequencing

This study is a prospective, randomized, multicenter clinical trial aiming to enroll 428 patients with non-muscle-invasive bladder cancer (NMIBC) from the Department of Urology at Jiangsu Provincial People's Hospital and its affiliated centers, who have undergone their initial transurethral resection and are scheduled for a second resection. Within 1-6 weeks after the first resection and prior to the second resection, 100ml of routine urine will be collected and sent within 24 hours to Beijing Genetron Health Clinical Laboratory Co., Ltd. for the extraction of urinary sediment DNA, which will then undergo genome-wide low-depth sequencing. Patients with positive test results will proceed with the second resection, while those with negative results will be randomly assigned in a 1:2 ratio to either the intervention group, which will not undergo a second resection, or the control group, which will undergo the second resection. All enrolled patients will be followed up for two years. The study will statistically analyze and compare the two-year recurrence-free survival rates between the two groups and evaluate the predictive capability of the test results for follow-up recurrence.

The Necessity of a Second Transurethral Resection in High-risk Non-muscle-invasive Bladder Cancer Patients With Negative Urine Biomarker After Initial Transurethral Resection

The goal of this clinical trial is to evaluate the efficacy of using a urine biomarker test to guide the decision-making process regarding the necessity of reTURBT in NMIBC patients. The main question aims to answer whether patients with negative urine biomarker tests can safely avoid reTURBT without compromising recurrence-free survival. Participants who have completed the initial TURBT and tested negative for the urine biomarker will be enrolled in the study. They will then be randomized 1:2 into two groups:Group A: Participants will not receive reTURBT and Group B: Participants will undergo reTURBT. Researchers will compare the RFS rates between Group A (no reTURBT) and Group B (reTURBT) to determine if the urine biomarker test can safely spare patients from unnecessary reTURBT.

Study on the Occurrence of Possible Relapses and on the Quality of Life in Patients Who Underwent TURBK.

A database has been created and will be used in which data will be collected in electronic format relating to adult patients who underwent one of the following endoscopic resection surgeries: TURBK, MAPPING, TURBK SECOND LOOK, BLADDER BIOPSIES.