Trial Title:
Risk-stratification Based Bladder-sparing Modalities for Muscle-invasive Bladder Cancer
NCT ID:
NCT05531123
Condition:
Bladder Cancer
Conditions: Official terms:
Urinary Bladder Neoplasms
Gemcitabine
Tislelizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
Tislelizumab 200 mg I.V. Q3W on the day 1
Arm group label:
Arm1(cCR=cT0, cTa)
Arm group label:
Arm2 (non-cCR)
Intervention type:
Drug
Intervention name:
gemcitabine and cisplatin
Description:
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
Arm group label:
Arm2 (non-cCR)
Intervention type:
Radiation
Intervention name:
Modified hypofractionation
Description:
- 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
Arm group label:
Arm2 (non-cCR)
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
85 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Yijun Shen, M.D.
Start date:
September 10, 2022
Completion date:
December 2024
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05531123
