Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

Exclusion Criteria

• •* Patients must have failed at least one (but no more than 2) prior line of systemic therapy in the advanced disease setting
• •* Patients who received adjuvant chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible; in this case, the adjuvant therapy will count as the minimum required one prior line of therapy; if patient received adjuvant treatment and had disease recurrence after 6 months, patients will only be eligible after failing one regimen of systemic chemotherapy used to treat the (unresectable or metastatic) disease recurrence
• •* If the patient has had decompression of the biliary tree within the last 14 days, stability of the bilirubin level needs to be confirmed with two measurements that are within 5 to 7 days of each other; (the second measurement must be obtained within 7 days prior to registration); both the first and second measurement must be =\< 2.5 x IULN; stability is defined as the second measurement being no more than one point higher than the first
• •Pancreatic cancer cohort specific criteria:
• •* Patients must have unresectable or metastatic pancreatic cancer
• •* Patients must have failed at least one prior line of therapy for metastatic or unresectable disease or have recurred within 6 months of completing adjuvant chemotherapy
• •* Patients with liver metastases must have \< 50% involvement of the liver
• •Patients may not be receiving any other investigational agents
• •Patients must not be nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
• •Any previous treatment with a hypomethylating agent, or with a PD1 or PD-L1 or anti-PD-L2 or anti-CTLA4 inhibitor, including durvalumab (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways); any immunomodulatory agent that is not described above should be cleared by the principal investigator (PI)
• •History of another primary malignancy except for:
• •* Malignancy treated with curative intent and with no known active disease \>= 3 years before the first dose of study drug
• •* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• •* Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ
• •* Controlled, superficial bladder carcinoma
• •* T1a or T1b or T1c prostate carcinoma treated with radiation \>= 1 year prior to study enrollment and prostate specific antigen (PSA) within normal limits (WNL) since treatment
• •* T2a or b prostate carcinoma treated curatively \>= 1 year prior to study enrollment and PSA undetectable since curative treatment
• •* Other early stage cancers that have a minimal chance of recurrence (i.e stage I endometrial cancer, cervical cancer, etc.) may be cleared by the PI
• •Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within 28 days prior to the first dose of study drug and within 6 weeks for nitrosourea or mitomycin C
• •Mean QT interval corrected for heart rate (QTc) \>= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia?s correction
• •Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid; live attenuated vaccines within 30 days of durvalumab dosing (ie, 30 days prior to the first dose, during treatment with durvalumab and for 30 days post discontinuation of durvalumab); inactivated vaccines, such as the injectable influenza vaccine, are permitted
• •Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more from previous anti-cancer therapy, except alopecia, hearing loss, peripheral neuropathy or non-clinically significant laboratory abnormalities
• •Any prior grade \>= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> grade 1
• •Active or prior documented autoimmune disease; subjects with vitiligo, Grave?s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
• •Active or prior documented inflammatory bowel disease (e.g., Crohn?s disease, ulcerative colitis)
• •History of primary immunodeficiency
• •History of allogeneic organ transplant
• •History of hypersensitivity to durvalumab, guadecitabine (SGI-110) or any excipient
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (defined as systolic blood pressure(SBP) \> 160 or diastolic blood pressure (DBP) \> 100 on 2 separate occasions separated by at least 24 hours), unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diathesis including any subject known to have evidence of human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• •Known history of previous clinical diagnosis of tuberculosis
• •History of leptomeningeal carcinomatosis or uncontrolled seizures
• •Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
• •Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
• •Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids
• •Presence of ascites that is not medically controlled or that required a therapeutic paracentesis within the last 3 months prior to initiation of study therapy
• •Known history or ongoing diagnosis of pneumonitis
• •* A history of hepatic encephalopathy within the past 12 months; patients on stable doses of lactulose for prophylaxis or as a result of previous hepatic encephalopathy (more than 12 months ago) are allowed (for HCC cohort only)
• •* A history of bleeding esophageal or gastric varices within the last 6 months prior to initiation of study therapy