NCT06351904Phase 1Recruiting
Ractigen Therapeutics. · GenesisCare North Shore, St Leonards, New South Wales
This is an open label, multi-center study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of RAG-01 in patients with NMIBC who have failed BCG therapy.
Eligibility: 18 Years to 75 Years · All · 1. Ability to understand the study and have signed the informed consent form;
2. Any adult ≥ 18 years old;
3. Pathologically confirmed high grade NMIBC defined as grade 2 or grade 3 disease;
4. Expected survival ≥ 6 months;
5. ECOG PS ≤2;
6. Sufficient organ functions, as defined below:
Investigations Hematology Absolute Neutrophil Count (ANC): ≥ 1.5 x 109/L Hemoglobin: ≥ 90 g/L Platelet: ≥ 100 x 109/L Liver Function Serum bilirubin: ≤ 1.25×ULN or 2.5×ULN（with Gilbert syndrome） AST \& ALT: ≤ 2.5×ULN Renal Function Creatinine Clearance (Cockcroft-Gault equation): ≥ 30 mL/min
7. Subject must be able to tolerate catheterization;
8. Female subject of childbearing potential and her spouse must use adopt effective contraception (non-pharmacological contraception required) from signing informed consent to within 6 months after the last instillation;
NCT05649306Phase IIRecruiting
Johns Hopkins University · Sibley Memorial Hospital, Washington D.C., District of Columbia
This research is being done to learn more about coping and survivorship of women with bladder cancer, specifically regarding psychosocial distress and sexual dysfunction. This study is a non-therapeutic study and will randomize participants to a standard of care group and education group. Patients in both groups will be asked to complete surveys regarding their mood and sexual function. Patients in the intervention group will be asked to complete attendance diaries regarding educational and support services utilized. Participants' clinical data will also be collected.
Eligibility: 18 Years to · Female · * Females with bladder cancer
* Willing to answer surveys regarding their psychosocial health and sexual health
NCT07359235Phase 1Recruiting
Tongji Hospital · Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei
Recombinant oncolytic adenovirus injection (KD01) is an oncolytic virus product. Its main component is a conditionally replicative recombinant human type 5 adenovirus, where part of the E3 region has been replaced with the gene encoding the tBid apoptotic protein.AK104 is a humanized bispecific antibody co-targeting PD-1 (Programmed Cell Death Protein 1) and CTLA-4 (Cytotoxic T-Lymphocyte-Associated Antigen 4)-two key immune checkpoint receptors. It is designed as a novel tetrameric construct that preferentially binds to tumor-infiltrating lymphocytes (TILs) co-expressing PD-1 and CTLA-4 in the tumor microenvironment (with higher avidity than in peripheral tissues).This is a Phase I clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of intravesical instillation of recombinant oncolytic adenovirus injection (KD01) in patients with bladder cancer.This study consists of Phase Ia and Phase Ib, where Phase Ia is a dose-escalation stage.The Phase Ia will include histopathologically confirmed non-muscle-invasive bladder cancer (NMIBC) patients with high-risk stratification (including extremely high-risk).The Phase Ib study will include two independent cohorts: Cohort A comprises high-risk non-muscle-invasive bladder cancer (NMIBC) patients (carcinoma in situ \[CIS\], with or without Ta/T1 stage lesions) who have shown no response to BCG. Cohort B will include T2-4aN0-1M0 stage bladder cancer patients (clinically localized muscle-invasive bladder urothelial carcinoma).
Eligibility: 18 Years to 75 Years · All · * 1.The Phase Ia will include histopathologically confirmed non-muscle-invasive bladder cancer (NMIBC) patients with high-risk stratification (including extremely high-risk). High-risk stratification criteria are defined as G3/high-grade tumors that meet any of the following criteria: carcinoma in situ (CIS); stage T1; diameter\>3 cm; multiple tumors; or recurrent tumors. The Phase Ib Cohort A will include BCG unresponsive NMIBC patients with carcinoma in situ \[CIS\], with or without Ta/T1 stage lesions, while Cohort B will include histopathologically confirmed muscle-invasive bladder cancer (cT2-4aN0-1M0).Note: BCG non-response is defined as meeting any of the following criteria: 1. Persistent or recurrent CIS within 12 months after completing adequate BCG treatment; 2. Recurrence of high-grade Ta/Tl disease within 6 months after completing adequate BCG treatment; 3. High-grade T1 disease at first evaluation after induction BCG treatment. (Adequate BCG treatment is defined as: Complete at least 5 out of 6 doses in the initial induction course. plus 2 out of 6 doses from the second induction course, or 2 doses from the 3-dose maintenance course.)
* 2.Excluding Phase Ib Cohort B, participants must either be medically ineligible for radical cystectomy as determined by urologists or have declined the procedure.
* 3.Age 18 to 75 (including 18 and 75).
* 4.Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 1.
* 5.Estimated survival time is ≥2 years.6.No dysfunction of major organs, including but not limited to hematopoietic function and cardiac, pulmonary,hepatic and renal function.
Hematologic system (no history of blood transfusion or hematopoietic growth factor treatment within 14 days)
1. Absolute neutrophil count (ANC)≥1.5×109/L
2. Platelets （PLT）≥75×109/L
3. Hemoglobin （Hb）≥90g/L
Hepatic function
1. Total bilirubin (TBIL)≤1.5× upper limit (ULN)
2. Alanine aminotransferase (ALT)≤3×ULN
3. Aspartate aminotransferase (AST)≤3×ULN
Renal function
1. Creatinine （Cr）≤1.5×ULN
2. Creatinine clearance (Ccr) (Calculation required only if creatinine exceeds 1.5×ULN)\>50 mL/min (calculated using the Cockcroft-Gault formula)
Coagulation function
1. Activated Partial Thromboplastin Time (APTT)≤1.5×ULN
2. International normalized ratio (INR)≤1.5×ULN
* 7.Premenopausal patients must have a negative blood pregnancy test during the screening period;they must agree to use reliable contraceptive methods (barrier contraceptive method or abstinence) with their partners during the trial and for at least 6 months after the last dose.
* 8.Patients must provide informed consent to the trial and voluntarily sign of a written informed consent form before participating in the trial.
NCT07036731NARecruiting
The First Affiliated Hospital with Nanjing Medical University · The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, Nanjing, Jiangsu
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.
Eligibility: 18 Years to 80 Years · All · * Patients with NMIBC who have completed the initial transurethral resection and are scheduled for a second resection, as recommended by guidelines or physician's choice:
1. Incomplete initial TURBT due to various reasons (including large tumor size, high risk of intraoperative bleeding, extensive tumor range, etc.), posing a risk of residual tumor;
2. Absence of muscle layer tissue in the initial resection specimen;
3. Post-initial resection pathology indicating T1 stage;
4. Post-initial resection pathology indicating G3/high-grade tumor, excluding pure carcinoma in situ;
* Ability to provide a 100ml routine urine sample within 1-6 weeks after the initial resection and before the second resection;
* Age ≥ 18 years;
* Willingness to provide basic clinical information, pathology, and subsequent - recurrence monitoring results;
* Willingness to sign the informed consent form.
NCT07475403Phase 2Recruiting
Tianjin Medical University Second Hospital · The Second Hospital of Tianjin Medical University, Tianjin
This study evaluates whether urinary tumor DNA (utDNA) testing, together with clinical, pathologic, and radiographic assessment, can help guide treatment discontinuation and active surveillance in patients with unresectable very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) treated with bladder-sparing systemic immunotherapy.
Participants receive systemic immune checkpoint inhibitor-based therapy every 3 weeks for an initial 3 cycles. Initial response assessment is performed using transurethral resection of bladder tumor (TURBT) and chest and abdominopelvic computed tomography (CT). Participants without progression to muscle-invasive, regional nodal, or distant metastatic disease then undergo post-TURBT urine cytology and urinary tumor DNA (utDNA) testing. Participants with both negative urine cytology and negative utDNA results receive an additional 3 cycles of systemic immunotherapy.
After the additional treatment, participants undergo repeat evaluation using cystoscopy with biopsy, urine cytology, utDNA testing, and chest and abdominopelvic CT. Participants with negative findings on cystoscopic biopsy, urine cytology, and utDNA testing, and without radiographic evidence of nodal or distant metastatic disease, discontinue systemic immunotherapy and enter an active surveillance phase with regular follow-up monitoring. Participants who do not meet these criteria continue further clinical management and follow-up according to institutional practice.
The study aims to determine whether a shortened duration of systemic immunotherapy guided by integrated molecular, clinical, pathologic, and radiographic response assessment can maintain favorable oncologic outcomes while reducing unnecessary treatment exposure in this high-risk population.
Eligibility: 18 Years to · All · 1. Age ≥18 years.
2. Histologically confirmed non-muscle-invasive urothelial carcinoma of the bladder classified as very-high-risk (VHR) according to EAU 2025 guideline criteria.
3. Disease considered unresectable by the investigator and multidisciplinary team, defined as complete tumor eradication by standard transurethral resection of bladder tumor (TURBT) being not feasible or unlikely to achieve adequate local control.
4. Patients who are ineligible or refuse for radical cystectomy, after discussion with the treating team.
5. At least one measurable or evaluable bladder lesion/documented residual disease suitable for response assessment by cystoscopy, TURBT/biopsy, pathology, urine cytology, and urinary tumor DNA (utDNA) testing.
6. ECOG performance status 0-2.
7. Adequate organ function, including:
Hematologic function: Absolute neutrophil count ≥1.5 × 10⁹/L, Platelet count ≥100 × 10⁹/L, Hemoglobin ≥9 g/dL Hepatic function: Total bilirubin ≤1.5 × ULN, AST ≤2.5 × ULN, ALT ≤2.5 × ULN Renal function: Serum creatinine ≤1.5 × ULN or Creatinine clearance ≥60 mL/min.
8. Ability to provide urine samples for utDNA testing and urine cytology during treatment and follow-up.
NCT06394570Phase 1, Phase 2Recruiting
University of Texas Southwestern Medical Center · UT Southwestern Medical Center, Dallas, Texas
STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for muscle invasive bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens:
Level 0: EV treatment followed by RT to the bladder Level 1: EV treatment with RT starting on Cycle 2, Day 15 Level 2: EV treatment with RT starting on Cycle 1, Day 15
Following completion of EV+RT neoadjuvant therapy, all subjects will undergo surgery as part of routine care.
Eligibility: 18 Years to · All · 1. Urothelial carcinoma of the urinary bladder stage cT2-4a (AJCC 8th edition) N0M0 planned for radical cystectomy. Mixed cell types with variant histologies (including squamous, plasmacytoid, adenocarcinoma, sarcomatoid, micropapillary, nested, and lipid cell variants) are allowed as long as any urothelial histology is present (i.e. -not 100% variant histology). Small cell/neuroendocrine component is excluded.
2. Ineligibility for cisplatin-based chemotherapy based on treating physician assessment and any of the following "Galsky criteria": renal insufficiency (Creatinine Clearance \<60ml/min by standard institutional calculation method), \>=grade 2 peripheral neuropathy, \>=grade 2 hearing loss, New York Heart Association (NYHA) class III heart failure; a combination of these; or patient refusal.
3. Age \>=18.
4. Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
5. Adequate organ and marrow function as defined below:
•Hematologic:
-Absolute neutrophil count (ANC) \>=1500/mm3
* Platelet count \>=100x109/L
* Hemoglobin ≥ 9 g/dL
•Hepatic:
* Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
•Renal:
* No end stage renal disease requiring dialysis allowed
6. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months following completion of study neoadjuvant therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
6a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
7.Ability to understand and the willingness to sign a written informed consent.
NCT05951179Phase 2Recruiting
Protara Therapeutics · Urology Centers of Alabama, Homewood, Alabama
TARA-002-101-Ph2 is an open-label study to investigate the safety and efficacy of intravesical instillation of TARA-002 in adults 18 years of age or older with high-grade CIS NMIBC (± Ta/T1).
The purpose of this Phase 2 study (TARA-002-101-Ph2) is to further assess the safety and efficacy of TARA-002 at the RP2D which has been established in the Phase 1a dose finding study (TARA-002-101-Ph1a).
This Phase 2 study includes participants with CIS NMIBC (± Ta/T1) with active disease, defined as disease present at last tumor evaluation (within 3 months) prior to signing the ICF.
Participants will be enrolled into one of 2 cohorts:
Cohort A:
* Participants with CIS (± Ta/T1) who are BCG naive, or
* Participants with CIS (± Ta/T1) who are BCG exposed and have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis
Cohort B:
* Participants who are BCG unresponsive
Eligibility: 18 Years to · All · * Male or female participants 18 years of age or older at the time of signing informed consent
* Participants who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry
* Central histologic confirmation of high-grade non-muscle invasive CIS (± Ta/T1) with active disease
* Participants who are BCG naive, or participants who are BCG exposed and have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis (Cohort A). Participants with CIS (± Ta/T1) who are BCG unresponsive.
NCT06704191Phase 1, Phase 2Recruiting
Mayo Clinic · Mayo Clinic in Florida, Jacksonville, Florida
This phase Ib/II trial compares the safety, tolerability and acceptability of intravesical chemotherapy given at home to in-clinic administration in patients with non-muscle invasive bladder cancer. Chemotherapy drugs, such as bacillus Calmette-Guerin (BCG), gemcitabine, docetaxel, and mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Standard of care chemotherapy for non-invasive bladder cancer is usually given directly into the bladder through a catheter (intravesical). This process requires numerous visits and can be disruptive to the lives of patients and caregivers. Bringing cancer care to the patients with in-home intravesical therapy may help reduce the disruption to daily lives. In-home intravesical chemotherapy may be safe and tolerable and may also be preferable to in-clinic administration in patients with non-muscle invasive bladder cancer.
Eligibility: 18 Years to · All · * PHASE IB ONLY: Female or male patients with histologically confirmed non-muscle invasive bladder cancer (stage Ta, Tis, or T1) who are currently receiving induction therapy with one of the following eligible intravesical treatment regimens
* Gemcitabine
* Sequential gemcitabine/docetaxel
* Bacillus Calmette-Guerin
* Mitomycin C
* PHASE II ONLY: Female or male patients with histologically confirmed non-muscle invasive bladder cancer (stage Ta, Tis or T1) who are receiving maintenance therapy with an eligible regimen
* PHASE IB ONLY: Able to be successfully catheterized and able to tolerate first dost of intravesical therapy in the outpatient clinic
* Residing within the area serviced by supplier network
* Residence either has Wi-Fi or cellular data network connection for virtual telehealth visits
* Age ≥ 18 years at time of registration
* Signed informed consent form by patient
* Willing and able to comply with the study protocol in the investigator's judgment
* Ability to complete questionnaire(s) by themselves or with assistance
* Willingness to follow birth control requirements for females and males of reproductive potential
NCT06896162NARecruiting
UNC Lineberger Comprehensive Cancer Center · Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
This is a hybrid decentralized, single-arm, interventional study designed to evaluate the impact of precision medicine navigation and reflexive expert review of next-generation sequencing (NGS) for patients with stage IV solid tumor malignancies (breast, lung, colorectal, and bladder cancers).
The purpose of this study is to investigate whether intervention from a centralized precision oncology navigator and expert review of NGS results by the precision oncology pharmacist will increase ordering of Level 1/2 genome informed therapy (GIT) compared to an estimated historical rate of 15%. Secondary endpoints will assess the impact of a centralized precision oncology navigator and expert review of NGS results on enrollment in biomarker-directed clinical trials and overall survival at 2 years after return of NGS results. The study will take approximately 12 months for enrolment and 2 years of follow-up after the date of NGS results.
Eligibility: 18 Years to · All · In order to participate in this study a subject must meet all of the eligibility criteria outlined below.
Inclusion Criteria
* Written informed consent was obtained to participate in the study and HIPAA authorization for release of personal health information.
* Subjects are willing and able to comply with study procedures based on the judgment of the investigator.
* Age ≥ 18 years at the time of consent.
* ECOG or Karnofsky Performance Status of 0-2.
* Documented Stage IV solid tumor malignancy: NSCLC, CRC, Breast or Bladder Cancer
* The treating provider deems Next Generation Sequencing (NGS) testing appropriate and plans to consider results in either first- or second-line therapy in the metastatic setting
* A genomic tumor test has not been ordered or has been ordered but not resulted.
NCT06929286Phase 3Recruiting
Memorial Sloan Kettering Cancer Center · Johns Hopkins University (Data Collection Only), Baltimore, Maryland
The purpose of this study is to compare the effectiveness of different FDA-approved/NCCN-recommended drug treatments for NMIBC. In particular, the FDA-approved drug nadofaragene firadenovec will be compared to usual care with other NCCN-recommended standard treatments for NMIBC (gemcitabine with or without docetaxel, mitomycin, re-treatment with BCG, or pembrolizumab).
Eligibility: 21 Years to · All · * 21 years of age or older
* Being treated for high-grade NMIBC (Tis, Ta, or T1) under the care of the participating treating urologists
* One or more prior induction course of BCG at any point in time and judgment by the treating urologist that BCG has failed
°Any amount of maintenance BCG is allowed
* In the previous 12 months, receipt of at least one instillation of any intravesical agent (induction or maintenance) or one administration of systemic therapy for NMIBC treatment
* An intravesical agent can include BCG or any other NMIBC treatment
* Up to 15 months from the last instillation is allowed for the treating physician to perform a transurethral resection of bladder tumor (TURBT) so long as there is evidence/suspicion of recurrent disease (by urinary cytology, imaging, or cystoscopy) within 12 months of last exposure to an intravesical agent.
* In the opinion of the treating urologist, there is no contraindication to treatment with nadofaragene firadenovec (i.e. hypersensitivity to IFNa, severe immunosuppression) and there is uncertainty over whether nadofaragene is better than "best usual care"
NCT07307456Phase 2Recruiting
Changhai Hospital · ChangHai Hospital, Shanghai, Shanghai Municipality
This is a single-center, prospective, open-label, non-randomized clinical study initiated and conducted by the Department of Urology, Shanghai Changhai Hospital. The Principal Investigators are Professor Zhang Zhensheng and Professor Chen Guanghua. The projected study period is from December 2025 to December 2028. This study aims to evaluate the efficacy and safety of toripalimab (a PD-1 inhibitor) combined with Bacillus Calmette-Guérin (BCG) intravesical instillation as adjuvant therapy following transurethral resection of bladder tumor (TURBT) in patients with high-risk/very high-risk non-muscle-invasive bladder cancer (NMIBC).
Bladder cancer is a common malignancy of the urinary system, with NMIBC accounting for approximately 75% of initial diagnoses. For high-risk patients who are unresponsive to or experience recurrence after BCG therapy, radical cystectomy remains the standard treatment. However, this procedure is associated with high rates of complications, mortality risk, and significantly negative impacts on quality of life. Therefore, exploring novel combination strategies that effectively reduce recurrence while preserving the bladder is of great clinical importance. This study is based on the successful application of immune checkpoint inhibitors in advanced urothelial carcinoma and recent Phase III trials (e.g., the CREST study) demonstrating the efficacy and safety of combining PD-1/PD-L1 inhibitors with BCG in treatment-naïve high-risk NMIBC. It seeks to investigate the potential of the domestic PD-1 inhibitor toripalimab in combination with standard BCG instillation.
The study plans to enroll 31 patients with histologically confirmed high-risk/very high-risk NMIBC who have not previously received immune checkpoint inhibitors or BCG therapy. All enrolled patients will first receive a single instillation of gemcitabine (2000mg), followed by the combination therapy phase: toripalimab (240mg, intravenous infusion, every 3 weeks for 8 cycles) combined with BCG intravesical instillation (induction phase for 6 weeks, maintenance phases at months 3 and 6). The primary efficacy endpoint is the pathological complete response (CR) rate at approximately 6 months after treatment initiation. Secondary efficacy endpoints include duration of CR, 6-month and 2-year event-free survival (EFS) rates, 1-year and 2-year cancer-specific survival (CSS) rates, time to radical cystectomy, and overall survival (OS). Safety endpoints encompass the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Statistical analyses will be based on the Full Analysis Set (FAS) and Per-Protocol Set (PPS). The sample size calculation for the primary endpoint (6-month CR rate) is based on historical data assumptions, employing a one-sided test. Safety analyses will include all patients who received at least one dose of study treatment. This study will strictly adhere to the principles of the Declaration of Helsinki, Chinese Good Clinical Practice (GCP) guidelines, and relevant regulations. The study protocol has been submitted for review and approval by the Institutional Review Board (IRB)/Ethics Committee. Written informed consent will be obtained from all patients prior to participation. This study aims to provide a new and potentially more effective bladder-preserving treatment option for patients with high-risk/very high-risk NMIBC and to evaluate the safety profile of this combination regimen.
Eligibility: 18 Years to 75 Years · All · 1. Age 18-75 years.
2. Patients with a pathological diagnosis of high-risk or very high-risk non-muscle-invasive bladder cancer (NMIBC) following transurethral resection or cystoscopic biopsy.
"High-risk patients" must meet any one of the following criteria:
1. All T1 high-grade (HG)/G3 without carcinoma in situ (CIS), excluding those in the very high-risk group.
2. All CIS patients, excluding those in the very high-risk group.
3. Ta low-grade (LG)/G2 or T1 G1 without CIS, accompanied by three risk factors.
4. Ta HG/G3 or T1 LG without CIS, accompanied by at least two risk factors.
5. T1 G2 without CIS, accompanied by at least one risk factor. "Very high-risk patients" must meet any one of the following criteria:
(1) Ta HG/G3 with CIS accompanied by three risk factors. (2) T1 G2 with CIS accompanied by at least two risk factors. (3) T1 HG/G3 with CIS accompanied by at least one risk factor. (4) T1 HG/G3 without CIS, accompanied by three risk factors. (Risk factors: age \>70 years; tumor diameter \>3 cm; multiple papillary carcinomas) 3. No prior treatment with therapies targeting PD-1, PD-L1, PD-L2, or CTLA-4, or other antibodies or drugs specifically targeting T-cell co-stimulation or checkpoint pathways (immune checkpoint blockers), or bacille Calmette-Guérin (BCG) therapy.
4\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Adequate organ function, defined as meeting the following criteria (within 14 days prior to enrollment, without transfusion or granulocyte colony-stimulating factor treatment): "Hematology": i. Absolute neutrophil count (ANC) ≥1,000/mm³ ii. Platelet count ≥75,000/mm³ iii. Hemoglobin ≥8.0 g/dL "Hepatic function": i. Total bilirubin ≤1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin \>1.5 × ULN.
ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
"Renal function": Creatinine clearance (CrCl) \>30 mL/min, calculated using the Cockcroft-Gault formula.
6\. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to enrollment, be willing to use effective contraception during the study period and for at least 6 months after the last dose of study drug (including chemotherapy agents and toripalimab). Male subjects with female partners of childbearing potential must agree to use effective contraception during the study period and for at least 6 months after the last dose.
7\. Subjects voluntarily agree to participate in the study by providing written informed consent, demonstrate good compliance, and are willing to cooperate with follow-up.
NCT06364956Phase 1, Phase 2Recruiting
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University · Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong
In order to explore the safety and antitumor efficacy of different doses of CDK4/6 inhibitor Palbociclib in combination with the Tislelizumab in platinum-refractory cT2-4aN0M0 bladder urothelial carcinoma, a phase Ib/II study was conducted.
This study will adopt a 3+3 design and include two predefined dose groups of palbociclib: 100mg QD, 125mg QD. Initially, Tislelizumab, 200 mg administered by intravenous infusion on Day 1 of each 21-day will be administered in combination. The trial will use the first cycle (28 days) as the observation period for tolerability, observing and evaluating the occurrence of DLTs after medication and determining the maximum tolerated dose/maximum administered dose (MTD/MAD) and recommended phase 2 dose (RP2D) of the combination therapy (30 patients) .
This study provide further evidence for improving the efficacy of neoadjuvant treatment forplatinum-refractory cT2-4aN0M0 bladder urothelial carcinoma and to offer new options for precision treatment of bladder cancer.
Eligibility: 18 Years to · All · 1. Voluntarily participate in this study, able to provide written informed consent and can understand and agree to comply with the requirements of the study and schedule of assessments.
2. Aged over 18 years on day of signing informed consent
3. Patients with urothelial bladder cancer, having residual lesions following TURBT surgery, staged cT2-T4aN0M0 as histologically confirmed and radiologically assessed based on the TNM Staging System for Bladder Cancer of American Joint Committee on Cancers (AJCC) ; predominantly histological classification of urothelial carcinoma (at least 50%) for patients with mixed-histology bladder cancer.
4. Patients with mutations or copy number variation (CNV) alterations, such as CDKN2A, CDKN2B CNV deletion, indicating the activation of cell cycle-related pathways.
5. ECOG Performance Status 0 or 1
6. Ineligible for Cisplatin treatment as judged by investigator. Patients who are ineligible for Cisplatin chemotherapy should meet at least one of the following criteria: ECOG performance status \> 1 or Karnofsky performance status 60% to 70%; creatinine clearance less than 60 mL/min; ≥ Grade 2 hearing loss according to NCI-CTCAE v5.0; ≥ Grade 2 neuropathy peripheral according to NCI-CTCAE v5.0; ≥ Grade 3 cardiac failure according to New York Heart Association Cardiac Function Classification
7. Patients will receive radical cystectomy following neoadjuvant therapy as assessed by investigator, meet surgical indication and are willing to receive the surgery.
8. Tumor tissue samples collected during TURBT must be available, and relevant pathological reports are required. Fresh surgical tissue samples or pathological slides are optional
9. Have adequate organ function as indicated by the following screening laboratory values (obtained ≤ 14 days prior to enrollment):
a.Patients must not be administered with growth factors ≤ 14 days prior to sampling for the screening tests of: i.Absolute neutrophil count ≥ 1.5 x 109/L ii.Platelets ≥ 90 x 109/L iii.Hemoglobin ≥ 90 g/L b.International normalized ratio or activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN).
c.Serum total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN, if Gilbert's syndrome or if indirect bilirubin concentrations were suggestive of extrahepatic source of the elevation).
e.Aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 x ULN f.Patients can tolerate major abdominal surgery as suggested by pulmonary function test results
10. Unpregnant females or females of childbearing potential must be willing to use a highly effective contraceptive method for the duration of the study, and ≥ 120 days after the last dose of Tislelizumab or chemotherapy agents, whichever is later, and have a negative urine or serum pregnancy test ≤ 7 days prior to enrollment.
