Bladder-sparing treatment options for muscle-invasive bladder cancer

A Prospective Phase II Study of Risk-stratification Based Bladder-sparing Modalities for Muscle-invasive Bladder Cancer After Chemotherapy Combined With PD-1 Antibody(Rebirth)

This study is testing a combination of chemotherapy and radiation treatments for people with muscle-invasive bladder cancer who want to avoid surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: immunotherapy, radiation, Nivolumab, Pembrolizumab, Tislelizumab, chemotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT05531123 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates bladder-sparing modalities for patients with muscle-invasive bladder cancer (MIBC) who wish to avoid radical cystectomy. It involves a combination of neoadjuvant chemotherapy, including Tislelizumab, gemcitabine, and cisplatin, along with modified hypofractionation radiation therapy. The study aims to assess the effectiveness of these treatments in achieving durable oncologic control and long-term survival while minimizing the need for surgical intervention. The trial focuses on a multidisciplinary approach to manage the complexities of treatment and follow-up.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 85 with muscle-invasive bladder cancer who have undergone TURBT and wish to preserve their bladder.

Not a fit: Patients with diffuse carcinoma in situ (CIS) lesions or those with significant organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide an effective alternative to radical cystectomy, preserving bladder function and improving quality of life for patients.

How similar studies have performed: Other studies have shown promising results with bladder-sparing therapies, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Male or female aged 18 and ≤ 85;
* People who want to protect their bladder;
* ECOG PS 0 2 points;
* Subject underwent TURBT surgery and imaging diagnosis of musculothelial invasive bladder urothelial carcinoma (histologic variation accepted, not diffuse CIS lesion);
* Accept maximum TURBT;
* Clinical stages T2-4A, N0-1, M0;
* Normal function of major organs (14 days prior to enrollment), i.e. meeting the following criteria:

  1. Blood routine examination criteria should be met (no blood transfusion and no granulocyte colony were received within 14 days before enrollment Stimulator therapy) :

     HB 90 g/L or higher The ANC acuity 1.5 x 109 / L PLT acuity 100 x 109 / L
  2. No functional organic disease, the following criteria should be met:

T-bil ≤1.5×ULN upper limit of normal value ALT and AST≤2.5×ULN If liver metastasis, ALT and AST≤5×ULN Estimated glomerular filtration rate (EGFR 60mL /min MdRD formula) International standardized ratio (INR), activated partial thrombin time aPTT ≤1.5× ULN(this standard is only applicable to patients who did not receive anticoagulant therapy; On anticoagulant therapy Patients should keep anticoagulants within the therapeutic range)

* Men who are fertile or women who are likely to become pregnant must use highly fertile men or women who are likely to become pregnant during the trial, Must be used in the testing process highly effective contraceptive methods (such as oral contraceptives, intrauterine contraceptive device, abstemious sexual desire or barrier contraception effective contraceptive methods (such as oral contraceptives, intrauterine contraceptive device, abstemious sexual desire or barrier contraceptive method combined with spermicide), and at the end of the treatment to birth control in combination with spermicide), and birth control for 12 months after the end of the treatment;
* Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up. The subjects voluntarily joined the study and signed informed consent with good compliance and follow-up.

Exclusion Criteria:

* Previously received anti-PD-1, anti-PD-L1, and anti-PD-L2 therapy;
* Known to be allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components;
* Received other antineoplastic therapy (including but not limited to corticosteroids) within 4 weeks prior to study therapy;
* Alcohol therapy, immunotherapy) or other clinical studies, or have not yet recovered from the previous toxicity (except 2 degree hair loss and 1 degree neurotoxicity);
* Women who are pregnant or breast-feeding, and women who wish to have children (pelvic radiation may cause ovarian function Premature aging);
* HIV positive;
* Patients with active hepatitis B or C; HBsAg or HBcAb positive patients were also detected with positive HBV DNA copy number (quantitative). The detection limit is 500IU/ml, or reaches the positive copy number detected by the research center); For such patients study screening must test for HBV DNA; HCV antibody test results are positive for patients, only when HCV RNA PCR test results. If it is negative, it can be included in this study;
* A clear history of active tuberculosis;
* Have active autoimmune diseases requiring systemic treatment within the past 2 years (e.g., using disease modulations);
* Section drugs, corticosteroids, or immunosuppressive drugs), allowing for relevant alternative therapies (e.g., thyroid Hormone, insulin, or physiological corticosteroid replacement therapy for renal or pituitary insufficiency);
* Other serious, uncontrolled comorbidities that may affect protocol compliance or interfere with interpretation of results;
* Diseases, including active opportunistic infections or advanced (severe) infections, uncontrolled diabetes, cardiovascular disease (Defined by the New York Heart Association classification as grade ⅲ or ⅳ heart failure, grade ⅱ or higher heart, visceral block, myocardial infarction in the past 6 months, unstable arrhythmia or instability, angina pectoris, cerebral infarction within 3 months, etc.) or lung diseases (interstitial pneumonia, obstructive pulmonary disease; History of pulmonary disease and symptomatic bronchial spasm);
* Received live vaccine within 4 weeks prior to the start of treatment;
* Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
* Those who have a history of abuse of psychotropic substances and cannot quit or have a history of mental disorders; Those who have a history of psychotropic drug abuse and cannot quit or have a history of mental disorders;
* Large pleural or ascites with clinical symptoms or requiring symptomatic management; Large pleural or ascites with clinical symptoms or symptomatic management;
* In the past five years have suffered from other malignant tumors, not cured but does not include has obvious cured malignant swell years suffered from other malignant tumors, not cured but does not include has obvious cure of malignant tumor, or can cure cancer, such as basal skin cancer or squamous cell cancer, limitations before low-risk tumor, or can be a cure for cancer, Such as basal or squamous cell skin cancer, localized low-risk prostate cancer, cervical carcinoma in situ or breast carcinoma in situ; Remarks: Localized low-risk prostate cancer (defined as adenocarcinoma, carcinoma in situ of the cervix, or carcinoma in situ of the breast; Remark: Limits (defined as low-risk prostate cancer stage for stage or less T2a, gleason score, gleason scores six points or less, and diagnosis of prostate cancer and prostate cancer diagnosis in the PSA 10 ng/mL or less (such as test (e.g., measurement) of the patients received radical amount) of the patients received radical surgery operation and without prostate specific antigen (and prostate specific antigen (P SA)) biochemical relapses biochemical relapses may participate in this study); Participants may participate in this study);
* Previous history of pelvic radiation therapy; Previous history of pelvic radiation therapy;
* Merged UTUC or urethral cancer
* May increase risks associated with study participation, or may interfere with study participation, according to the researchers. Any other serious, acute or chronic medical or mental illness or laboratory abnormality that may increase the risk associated with study participation or that may interfere with the interpretation of study results or the interpretation of laboratory findings.

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Yijun Shen, M.D.

Conditions Bladder Cancer