Non-Muscle Invasive Bladder Urothelial Carcinoma
Conditions
Brief summary
The goal of this clinical trial is to learn the dose-limiting toxicity of the new combined treatment with irinotecan liposomes (intravenous injection) and epirubicin (intravesical instillation) in anthracyclines treatment-failed non-muscle invasive bladder cancer adults. It will also learn if the combined treatment works to treat these patients. Additionally, the safety and biological mechanisms of the combined treatment will also be explored. The main questions it aims to answer are: * Does the combined treatment of irinotecan liposomes and epirubicin reverse anthracyclines resistance of participants? * What medical problems do participants have after taking the combined treatment of irinotecan liposomes and epirubicin? * What biological mechanisms underlie the effect of irinotecan liposomes on anthracyclines resistance? Participants will be classified into Arm A and Arm B. * Arm A: Participants will receive an intravenous injection of irinotecan liposomes once every two weeks for one month, along with intravesical instillation of epirubicin once a week for one month. Patients will be evaluated by two professional urologists; those with a complete response or partial response will undergo transurethral resection of bladder tumor (TURBT) and intravesical therapy. Patients with stable or progressive disease will receive subsequent treatment at the investigator's discretion. Participants are required to visit the hospital for physical examination every two weeks. * Arm B: In the first month after TURBT surgery, participants will receive intravenous injection of irinotecan liposomes once every two weeks for one month, and intravesical instillation of epirubicin once a week for one month, followed by once a month for six months. Participants are required to visit the clinic for physical examination once every two weeks in the first month, and once every three months after that. * Keep a diary of their symptoms during the study period.
Interventions
In the A arm, the combined treatment with irinotecan liposome (intravenous injection, once every two weeks for 1 month, dose increasing regimen: 37.6 mg/m2 and 56.5mg/m2) and epirubicin (intravesical instillation, once a week for 1 month, 50 mg) is in the neoadjuvant therapy phase before TURBT surgery.
Sponsors
First Affiliated Hospital of Chongqing Medical University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
It is a double cohort study, the two cohorts are incomparable. If the recurrent tumor can't be excised by transurethral resection of bladder tumor (TURBT), the participant will enter the A arm, and if the recurrent tumor can be excised by TURBT, the participant will enter the B arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* cTa-cT1N0M0 patients with non-muscle invasive urothelial carcinoma * Tumor recurrence occurred after anthracyclines treatment * Systemic chemotherapy had not been used * Tumor is measurable according to New response evaluation criteria in solid tumours: Revised RECIST guideline * ECOG (ZPS, 5-point scale) 0-1
Exclusion criteria
* Age less than 18 years * Patients with severe cardiac, cerebral, hepatic, or renal disease * Severely malnourished patients * Patients with mental illness and those without insight and unable to express exactly * Combined with malignant tumors of other organs * Systemic infectious diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone marrow suppression (Grade four) | 4 weeks | 1. Absolute Neutrophil Count \< 0.5\*10\^9/L 2. Platelet \<25\*10\^9/L 3. leukocyte \<1.0\*10\^9/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and adverse events | 2 months | The description of adverse events will be coded according to MedDRA terminology and graded according to NCI-CTCAE v5.0. |
| Objective remission rate (Arm A available) | 4 weeks | The proportion of patients with complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) after treatment was calculated according to the recognized response evaluation criteria (such as New response evaluation criteria in solid tumours: Revised RECIST guideline , version 1.1). CR: All tumor target lesions disappeared and no new lesions appeared. PR: The sum of maximum diameter of tumor target lesions decreased by ≥30%; SD: The sum of the maximum diameter of tumor target lesions did not shrink to PR, or increase to PD; PD: The sum of the maximum diameters of tumor target lesions increases at least ≥20%, or new lesions appear. |
| Recurrence-free survival (Arm B available) | 3-6 months | The time from TURBT surgery to recurrence or the end of follow-up. |
| BLM Lactylation of tumor tissues | 4 weeks | The BLM lactylation of tumor tissue |
| The levels of DNA double-strand break and homologous recombination repair in tumor tissues | 4 weeks | The levels of DNA double-strand break and homologous recombination repair in tumor tissues are detected |
Countries
China
Contacts
Primary ContactXin Gou, Professor
Outcome results
None listed