|Age:||18 years or older|
|Keywords:||bladder cancer, bladder removal, muscle-invasive bladder cancer|
|Type:||Drug study, Phase 2|
The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.
Documentation of Disease
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 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
One focus of muscle-invasive bladder cancer and/or a tumor <5 cm in size
No clinical or radiographic evidence for locally advanced or metastatic disease
No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)
No prior radiation therapy to the bladder
No major surgery or radiation therapy <4 weeks of registration
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.
Age ≥ 18 years
ECOG Performance Status 0-1
Required Initial Laboratory Values:
Absolute Neutrophil Count (ANC) ≥ 1,000/mm3
Platelet Count ≥ 100,000/mm3
Calculated creatinine clearance ≥ 55 mL/min
Total Bilirubin ≤ 1.5 x upper limit of normal (ULN)
(For patients with documented Gilbert’s syndrome Bilirubin ≤ 3 x ULN)
AST / ALT ≤ 2.5 x ULN
Alkaline Phosphatase ≤ 2.5 x ULN
No hydronephrosis refractory to urinary diversion
No evidence of NYHA functional class III or IV heart disease
No ongoing cardiac dysrhythmias of NCI 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 marrowsuppressive 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 nontherapeutic 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.
Patients must have completed 4 or more cycles of protocol-directed chemotherapy.
Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pretreatment TURBT DNA
Cystoscopy and imaging performed to determine stage/treatment assignment.
Have any questions or want to learn more? Leave your contact details below and the research team will reach out to you.