Urothelial, Muscle Invasive and Locally Advanced (A031501)

For a patient to be eligible for participation in this study, all of the following criteria must apply.

Pre-Registration Eligibility Criteria

• Histologically confirmed muscle-invasive urothelial carcinoma of the bladder or upper tract; variant histology allowed as long as urothelial carcinoma is predominant (> 50%); pure small-cell carcinoma is excluded
• Paraffin tissue samples obtained by transurethral resection of muscle-invasive bladder tumor, upper tract resection, cystectomy/nephrectomy/ureterectomy, or nephroureterectomy must be available; this specimen submission is mandatory prior to registration as results will be used for stratification
• 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+
• Patient must have had radical surgical resection of their bladder cancer >= 4 weeks but =< 16 weeks prior to pre-registration
• No invasive cancer at the surgical margins
• No evidence of residual cancer or metastasis after surgery
• No 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) (+) patients are eligible as long as they have: cd4 > 200, undetectable viral load and on highly active antiretroviral therapy (HAART) therapy
• 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 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 pregnant and not nursing
• 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
• Creatinine =< 2.0 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance >= 30 mL/min
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• 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; 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

To learn more, visit ClinicalTrials.Gov

Study Type

Phase III

Principal Investigator(s)

Michael Humeniuk, MD

Sponsor(s)

National Cancer Institute (NCI)