Phase III Randomized Adjuvant Study of MK-3475 (Pembrolizumab) in Muscle Invasive and Locally Advanced Urothelial Carcinoma (AMBASSADOR) Versus Observation
This phase III trial studies how well pembrolizumab works in treating patients with bladder cancer that has spread into the deep muscle of the bladder wall (muscle-invasive) or urothelial cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Monoclonal antibodies recognizing and blocking checkpoint molecules can enhance the patient's immune response and therefore help fight cancer. Pembrolizumab is one of the monoclonal antibodies that block the PD-1 axis and can interfere with the ability of tumor cells to grow.
- "PRE-REGISTRATION ELIGIBILITY CRITERIA
Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, urethra, upper tract, or lymph node positive (LN+) disease
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- variant histology allowed as long as urothelial carcinoma is predominant (any amount of squamous differentiation is allowed)
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- any component of neuroendocrine carcinoma is excluded
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The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized
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- 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
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- patients who have had a partial cystectomy as definitive therapy are not eligible
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No gross cancer at the surgical margins
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- microscopic invasive urothelial carcinoma positive margins are allowed
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- carcinoma in situ (CIS) at margins is considered negative margins
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No evidence of residual cancer or metastasis after surgery
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- patients with upper tract urothelial carcinoma must have a negative cystoscopy within 3 months prior to pre-registration
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- if the bladder has been removed a cystoscopy is not required
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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)"
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- No gross cancer at the surgical margins
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- microscopic invasive urothelial carcinoma positive margins are allowed
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- carcinoma in situ (CIS) at margins is considered negative margins
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No evidence of residual cancer or metastasis after surgery
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- patients with upper tract urothelial carcinoma must have a negative cystoscopy within 3 months prior to pre-registration
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- if the bladder has been removed a cystoscopy is not required
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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)
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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
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- 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
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- systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis
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- 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
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- human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
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No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years
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
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- 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
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- seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed
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- 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
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- 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
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- 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
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- after sites receive the confirmation e-mail from Alliance they can register the patient
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