RESOLVE : A Phase I Trial of Tremelimumab + Durvalumab(MEDI4736)+ Belinostat in Urothelial Carcinoma
This phase I trial studies the side effects and best dose of belinostat when given together with durvalumab in treating patients with urothelial cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable) and has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Belinostat is a potential anti-cancer drug, known as a histone deacetylase (HDAC) inhibitor, which means that belinostat stops the activity of HDAC enzymes (an enzyme is a protein that in small amounts can speed up a biological reaction). HDAC enzymes play an important role in cell growth and cell death. Giving durvalumab and belinostat may improve the body's ability to fight cancer.
• Male or female subject aged \>= 18 years
• Histologically confirmed urothelial carcinoma with metastatic disease or with unresectable, locally advanced disease. Variant histology, including, but not limited to, neuroendocrine, sarcomatoid, and squamous differentiation are permitted to enroll
• Patients must meet one or more of the following criteria:
‣ Has progressed on at least one prior therapy; or
⁃ Has declined standard therapy; or
⁃ Is not a suitable candidate for standard therapy
⁃ The discussion regarding the choice of standard therapy offered, if available, and patient's choice and reason(s) to decline standard therapy should be documented clearly in the research chart.
⁃ Patients may have progressed on immune checkpoint inhibitor therapy
• Body weight \> 30 kg
• Subject must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by computed tomography (CT) or magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelet count \>= 100,000/mm\^3
• Hemoglobin \>= 10 g/dL
• Total Bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
‣ Patients with liver metastases will be allowed to enroll with AST and ALT levels =\< 5 x ULN
• Estimated creatinine clearance \>= 30 mL/min by Cockcroft-Gault formula
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
‣ Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
⁃ Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
• Highly effective contraception for both male and female subjects throughout the study and at least 4 months after last study treatment administration
• Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 from toxicities related to any prior treatments, unless adverse event (AE)(s) are clinically non-significant and/or stable on supportive therapy
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
• Estimated life expectancy of at least 12 weeks