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

Running, not enrolling · Phase 1

Conditions studied: Extrahepatic Bile Duct Adenocarcinoma, Biliary Type, Gallbladder Adenocarcinoma, Biliary Type, Metastatic Pancreatic Adenocarcinoma, Recurrent Cholangiocarcinoma, Recurrent Gallbladder Carcinoma, Recurrent Hepatocellular Carcinoma, Recurrent Intrahepatic Cholangiocarcinoma, Recurrent Pancreatic Carcinoma, Stage III Gallbladder Cancer AJCC V7, Stage III Hepatocellular Carcinoma AJCC v7, Stage III Intrahepatic Cholangiocarcinoma AJCC v7, Stage III Pancreatic Cancer AJCC v6 and v7, Stage IIIA Gallbladder Cancer AJCC v7, Stage IIIA Hepatocellular Carcinoma AJCC v7, Stage IIIB Gallbladder Cancer AJCC v7, Stage IIIB Hepatocellular Carcinoma AJCC v7, Stage IIIC Hepatocellular Carcinoma AJCC v7, Stage IV Gallbladder Cancer AJCC v7, Stage IV Hepatocellular Carcinoma AJCC v7, Stage IV Pancreatic Cancer AJCC v6 and v7, Stage IVA Gallbladder Cancer AJCC v7, Stage IVA Hepatocellular Carcinoma AJCC v7, Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7, Stage IVB Gallbladder Cancer AJCC v7, Stage IVB Hepatocellular Carcinoma AJCC v7, Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7, Unresectable Gallbladder Carcinoma, Unresectable Pancreatic Carcinoma

In brief

This phase Ib trial studies the side effects and best dose of guadecitabine and how well it works when given together with durvalumab in treating patients with liver, pancreatic, bile duct, or gallbladder cancer that has spread to other places in the body. Guadecitabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as durvalumab, may block tumor growth in different ways by targeting certain cells. Giving guadecitabine and durvalumab may work better in treating patients with liver, pancreatic, bile duct, or gallbladder cancer.

Key facts

Study ID: NCT03257761
Run by: University of Southern California
People needed: 55
Starts: 2018-02-07
Expected to finish: 2026-12-31
Last updated by the study team: 2026-06-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Absolute neutrophil count (ANC) >= 1.5 x 10\^9/L (> 1500 per mm\^3) except for patients with HCC for whom ANC >= 1000 per mm\^3 is allowed
Platelet count >= 100 x 10\^9/L (> 100,000 per mm\^3), except for patients with HCC for whom a platelet count > 60,000 per mm\^3 is allowed
Hemoglobin >= 8.0 g/dL; if patients have a hemoglobin level below 8, blood transfusion is allowed to meet the eligibility criteria as long as post transfusion hemoglobin is maintained at >= 8.0 g/dL for 7 days or longer
Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2.5 x institutional upper limit of normal unless liver metastases are present or unless patient is known to have chronic liver disease (hepatitis) in which case AST and ALT must be =< 5 x institutional upper limit of normal (IULN)
Serum bilirubin =< 2.5 x institutional upper limit of normal (ULN)
Serum albumin >= 2.5 g/dL
Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: >= 60 years old and no menses for >= 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry
Ability to understand a written informed consent
Signed written informed consent and Health Insurance Portability and Accountability Act (HIPAA) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
Patients must have measurable disease as defined by RECIST 1.1 criteria
Hepatocellular carcinoma cohort specific criteria:
Patients must have a histologically proven diagnosis of hepatocellular carcinoma that is not amenable to curative surgical therapeutic options
Patients must not be good candidates for locoregional therapy as determined by the investigator (ie diffuse multifocal disease, vascular involvement, etc)
Patients must have had evidence of radiologic progression on sorafenib or have had intolerance to sorafenib as defined by the recurrence of clinically significant toxicities despite a minimum of one dose reduction and appropriate supportive care; patients who refuse sorafenib are eligible with documentation of refusal by the treating physician
Patients may have received other treatment for HCC such as embolization, chemoembolization, intra-arterial chemotherapy, ethanol injection, ablative therapy, cryosurgery, or other locoregional or targeted therapy
Patients must have a Child Pugh score of 7 points or less
International normalized ratio (INR) =< 2.3 or prothrombin time =< 6 seconds above control
Patients with hepatitis B infection must be on appropriate anti-viral therapy

You may not qualify if…

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

Where it is running

USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian — Newport Beach, California, United States
Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States

Full record on ClinicalTrials.gov

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