Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer
A Phase Ib Study of Guadecitabine (SGI-110) and Durvalumab (MEDI 4736) in Patients With Advanced Hepatocellular Carcinoma, Pancreatic Adenocarcinoma, and Cholangiocarcinoma/Gallbladder Cancer
3 other identifiers
interventional
55
1 country
3
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2018
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 19, 2017
CompletedFirst Posted
Study publicly available on registry
August 22, 2017
CompletedStudy Start
First participant enrolled
February 7, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 27, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
ExpectedJune 1, 2026
May 1, 2026
3.6 years
August 19, 2017
May 27, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events
Graded according to Common Terminology Criteria for Adverse Events version 4.03.
Up to 56 days
Tumor response (dose expansion)
Will be calculated by the percentage of patients having complete or partial response among all patients who have been treated at maximum tolerated dose/recommended phase II dose in each cohort. Will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST).
Up to 2 years
Secondary Outcomes (2)
Overall survival
From start of treatment until death due to any cause, assessed up to 2 years
Progression-free survival
From start of treatment to time of progression per RECIST 1.1 or death whichever comes first, assessed up to 2 years
Study Arms (1)
Treatment (guadecitabine, durvalumab)
EXPERIMENTALPatients receive guadecitabine SC QD on days 1-5 and durvalumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Eligibility Criteria
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
- +19 more criteria
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
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Southern Californialead
- National Cancer Institute (NCI)collaborator
- Van Andel Research Institutecollaborator
Study Sites (3)
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anthony El-Khoueiry, MD
University of Southern California
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 19, 2017
First Posted
August 22, 2017
Study Start
February 7, 2018
Primary Completion
September 27, 2021
Study Completion (Estimated)
December 31, 2026
Last Updated
June 1, 2026
Record last verified: 2026-05