Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- PRE-REGISTRATION ELIGIBILITY CRITERIA
- Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, urethra,
upper tract, or lymph node positive (LN+) disease; variant histology allowed as long
as urothelial carcinoma is predominant (any amount of squamous differentiation is
allowed); any component of neuroendocrine carcinoma is excluded
- Paraffin tissue samples obtained by transurethral resection of muscle-invasive bladder
tumor, upper tract resection, or radical
cystectomy/nephrectomy/ureterectomy/nephroureterectomy/cystoprostatectomy or
urethrectomy must be available; this specimen submission is mandatory prior to
registration as results will be used for stratification; specimens from
radical/definitive surgery (radical cystectomy/nephrectomy/ureterectomy
/nephroureterectomy/cystoprostatectomy and LN dissection) are preferred over
transurethral resection, if available
- Patient must fit into one of the following three categories:
- Patients who received neoadjuvant chemotherapy and pathologic stage at surgical
resection is >= pT2 and/or N+ OR
- Patients who are not cisplatin-eligible (according to >= 1 of the following
criteria: Eastern Cooperative Oncology Group [ECOG] performance status of 2,
creatinine clearance < 60 mL/min, grade >= 2 hearing loss, grade >= 2 neuropathy,
or New York Heart Association class III heart failure and pathologic stage at
surgical resection is >= pT3 or pN+) OR
- Patients that decline adjuvant cisplatin-based or other systemic chemotherapy
based on an informed discussion with the physician and pathologic stage at
surgical resection is >= pT3 or pN+
- The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized;
patient must have had radical cystectomy (cystoprostatectomy for men) and lymph node
dissection (for bladder primary), or nephrectomy, nephroureterectomy or ureterectomy
(for uppertract tumors) or urethrectomy (in addition to a radical cystectomy-either
simultaneously or in the past) >= 4 weeks but =< 16 weeks prior to pre-registration;
patients who have had a partial cystectomy as definitive therapy are not eligible
- No gross cancer at the surgical margins; microscopic invasive urothelial carcinoma
positive margins are allowed; carcinoma in situ (CIS) at margins is considered
negative margins
- No evidence of residual cancer or metastasis after surgery; patients with upper tract
urothelial carcinoma must have a negative cystoscopy within 3 months prior to
pre-registration; if the bladder has been removed a cystoscopy is not required
- No metastatic disease (or radiologic findings "concerning" for metastatic disease) on
cross-sectional imaging (according to Response Evaluation Criteria in Solid Tumors
[RECIST] version [v]1.1 criteria)
- No active autoimmune disease or history of autoimmune disease that might recur, which
may affect vital organ function or require immune suppressive treatment including
systemic corticosteroids; these include but are not limited to patients with a history
of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating)
neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease
such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma,
inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients
with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or
phospholipid syndrome because of the risk of recurrence or exacerbation of disease;
human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible
- No current pneumonitis or prior history of non-infectious pneumonitis that required
steroids within the previous 5 years
- Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus,
thyroiditis managed with replacement hormones including physiologic corticosteroids
are eligible
- Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and
psoriasis controlled with topical medication and patients with positive serology, such
as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the
presence of target organ involvement and potential need for systemic treatment but
should otherwise be eligible
- No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
detected)
- No live vaccine within 30 days prior to the first dose of study drug; examples of live
vaccines include, but are not limited to, the following: measles, mumps, rubella,
varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG),
and typhoid vaccine; seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist)
are live attenuated vaccines and are not allowed
- No postoperative/adjuvant systemic therapy
- No prior treatment with any therapy on the PD-1/PD-L1 axis
- No treatment with any other type of investigational agent =< 4 weeks before
pre-registration
- No major surgery =< 4 weeks before pre-registration
- No radiation therapy =< 4 weeks before pre-registration
- No neoadjuvant chemotherapy =< 4 weeks before pre-registration
- Not currently requiring hemodialysis
- Age >= 18 years
- Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown
- ECOG performance status =< 2
- Absolute neutrophil count (ANC) >= 1,200/mm^3
- Leukocytes >= 3,000/ mm^3
- Platelet count >= 75,000/mm^3
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Bilirubin for patients with Gilbert's =< 3.0 x ULN
- Calculated (calc.) creatinine clearance >= 30 mL/min (using either Chronic Kidney
Disease Epidemiology Collaboration [CKD-EPI] equation or Cockcroft-Gault formula)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit
of normal (ULN)
- Serum albumin >= 2.8 g/dL
- For women of childbearing potential only: a negative urine or serum pregnancy test
done =< 7 days prior to pre-registration is required
- REGISTRATION ELIGIBILITY CRITERIA: Results of central PD-L1 testing available; Q2
Solutions will forward the PD-L1 results to the statistical center and the statistical
center will notify the site that the result is available; since the results with be
blinded to the site the notification from the Alliance registration/randomization
office will serve as a confirmation of this eligibility criteria; after sites receive
the confirmation e-mail from Alliance they can register the patient