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A031501: Urothelial; muscle invasive and locally advanced

Phase III Randomized Adjuvant Study of MK-3475 (Pembrolizumab) in Muscle Invasive and Locally Advanced Urothelial Carcinoma (AMBASSADOR) Versus Observation

Objective

Overview

This randomized phase III trial studies how well pembrolizumab works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Key Inclusion Criteria

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

Phase: III

Learn More

ClinicalTrial.Gov

                          IRB Protocol Number
                          A031501
                          Principal Investigator(s)
                          Michael Humeniuk, M.D.

                          Clinical Trial Categories

                          • Genitourinary Cancer
                          Sponsor(s)
                          National Cancer Institute (NCI)
                          Contact
                          Christy Moore, RN at 864-560-1033
                          or cmoore@gibbscc.org
                          How to Participate

                          Christy Moore, RN

                          864-560-1033

                          cmoore@gibbscc.org

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