رادار التجارب السريرية

Step 1 Patient Registration Eligibility Criteria

Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration

20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable

Clinical stage T2-T4aN0/xM0 disease

Medically appropriate candidate for radical cystectomy as assessed by surgeon

No concomitant multifocal carcinoma in situ; a single focus is allowed

A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and TURBT will take precedence over radiographic measurements of tumor size.

No clinical or radiographic evidence for locally advanced or metastatic disease

No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5 years (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed. Intravesical chemotherapy is allowed.

No prior radiation therapy to the bladder or prostate

No major surgery or radiation therapy =< 4 weeks of registration (TURBT is allowed).

Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required

Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Absolute neutrophil count (ANC) >= 1,000/mm^3

Platelet count >= 100,000/mm^3

Calculated creatinine clearance ≥ 55 mL/min using formula per institutional standard or investigator's discretion. The same formula should be used to calculate all subsequent creatinine clearances.

Total bilirubin =< 1.5 x upper limit of normal (ULN)

* (For patients with documented Gilbert's syndrome Total Bilirubin =< 3 x ULN)

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN

Alkaline phosphatase =< 2.5 x ULN

No evidence of New York Heart Association (NYHA) functional class III or IV heart disease

No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2

No pre-existing sensory grade >= 2 neuropathy

No pre-existing grade >= 2 hearing loss

No serious intercurrent medical or psychiatric illness, including serious active infection

None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack

No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated

No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study

No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed

No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible

Step 2 Patient Registration Eligibility Criteria

Patients must have completed 4 or more cycles of protocol-directed chemotherapy and DDR gene results must be available

Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)

Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)

Cystoscopy and imaging performed to determine stage/treatment assignment