Risk-stratification Based Bladder-sparing Modalities for Muscle-invasive Bladder Cancer

NCT05531123 | Recruiting Phase 2

• 1 other identifier: ReBirth-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant chemotherapy plus radical cystectomy is the standard if care for cisplatin-eligible patients with MIBC. Developments in the last two decades suggest that bladder sparing therapy may be a valuable alternative to radical cystectomy. Currently, well-documented TMT regimens, which include complete transurethral resection of bladder tumor (TURBT), chemotherapy, and radiation therapy, demonstrated durable oncologic control and long-term survival in selected patients. Nevertheless, TMT has not been widely used in clinical practice. On the one hand, due to the complexity of TMT, multiple clinical departments are required to cooperate in the assessment, treatment and follow-up of patients. On the other hand, concerns about tumor recurrence, lack of surgical intervention in regional lymph nodes, and organ dysfunction due to the treatment of large doses of pelvic radiation have reduced the clinical acceptance of TMT. In recent years, immunocheckpoint inhibitors such as PD-1/L1, including Nivolumab, Pembrolizumab, and Tislelizumab, have proven to be promising immunotherapy approaches for advanced urothelium cancer, leading to breakthroughs in the treatment of advanced urothelium cancer. Immunocheckpoint inhibitors also showed positive efficacy in patients who did not respond to BCG treatment during perioperative period. Therefore, immunotherapy can be another means of bladder preservation after surgery, chemotherapy and radiotherapy. However, bladder sparing target population is still unclear, among which, the NCCN guidelines recommend patients suitable for bladder preservation: T2-3N0M0, single lesion (longest diameter less than 6 cm), histological type of urothelial carcinoma, no CIS, and no hydronephrosis. Therefore, the focus of bladder preservation treatment is not only on the treatment before and during bladder preservation, but also on maximizing the follow-up treatment of TURBT and exploring its long-term benefits based on response to systematic treatment before maximized TURBT.

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• BIDFS at one year

  BIDFS, bladder intact disease free survival, was defined as the time from the start of regimen until MIBC recurrence, regional pelvic recurrence, distant metastasis, bladder cancer-related death, or cystectomy.

  one year

Secondary Outcomes (4)

• MFS at two years

  two years

• BIDFS at two years

  two years

• Treatment-related adverse events

  two years

• cCR after first treatment stage

  two years

Other Outcomes (1)

• utDNA

  two years

Study Arms (2)

Arm1(cCR=cT0, cTa)

EXPERIMENTAL

Drug: Tislelizumab

Arm2 (non-cCR)

EXPERIMENTAL

Drug: Tislelizumab; Drug: gemcitabine and cisplatin; Radiation: Modified hypofractionation

Interventions

Tislelizumab DRUG

Tislelizumab 200 mg I.V. Q3W on the day 1

Arm1(cCR=cT0, cTa); Arm2 (non-cCR)

gemcitabine and cisplatin DRUG

Cisplatin 70mg/m2 I.V. Q3W on the day 1, dose fractionation is allowed ;Gemcitabine 1000mg/m2 I.V. Q3W on the day 1 and day 8

Arm2 (non-cCR)

Modified hypofractionation RADIATION

* Whole bladder 44Gy / 16fractionation (If N1: Whole bladder + Pelvic nodes 44Gy / 16fractionation) (Positive lymph nodes can be dosed to the maximum tolerable dose) * Tumor boost 11Gy / 4fractionation * Radiosensitizing chemotherapy: DDP 75-80 mg/m2 weekly Q3W

Arm2 (non-cCR)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

tislelizumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Yijun Shen, M.D.

CONTACT

862164175590; yijunshen@urocancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: September 7, 2022
• Study Start: September 10, 2022
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 12, 2024

Record last verified: 2024-07

Locations

CN (1)