Leveraging epigenetic alterations in pancreatic ductal adenocarcinoma for clinical applications.
Jorg Tost, Secil Ak-Aksoy, Daniele Campa...
https://pubmed.ncbi.nlm.nih.gov/39863139Actively Recruiting
Phase 1
Phase 2
Age: 18Years +
All Genders
ID05053971
Phase Ib/II Study of ZEN003694 and Entinostat in Advanced and Refractory Solid Tumors
Led by National Cancer Institute (NCI) · Updated on 2026-04-13
49
Participants Needed
3
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, side effects, and optimal dose of a combination of two drugs, entinostat and ZEN003694, in patients with advanced or treatment-resistant solid tumors. Entinostat is a histone deacetylase inhibitor that may block enzymes needed for tumor growth, while ZEN003694 inhibits bromodomain and extra-terminal proteins to potentially slow tumor cell growth. This phase I/II trial aims to test the combination therapy's safety and effectiveness, especially in advanced or refractory pancreatic cancer. During the study, patients receive entinostat orally once a week and ZEN003694 orally on an intermittent schedule across 28-day cycles. The earlier daily dosing phases are no longer used. Patients undergo core needle biopsies at specific times and have CT scans throughout the study. Treatment continues until disease progression or unacceptable side effects occur. Participants will have regular assessments including physical exams, CT imaging, laboratory tests, and biopsies to monitor tumor response and safety. Researchers will measure maximum tolerated dose, overall response rate, progression-free survival, and overall survival. After treatment ends, patients are followed for 30 days to monitor safety and outcomes. The study also explores effects on tumor biology and gene expression through blood and tissue analyses.
CONDITIONS
Brief Title
Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Patients must have advanced or refractory solid tumors and meet standard treatment requirements
- Phase 2 patients must have locally advanced, unresectable or metastatic pancreatic cancer refractory to standard therapy
- Measurable disease per RECIST 1.1 criteria
- Received at least one standard treatment for metastatic disease
- Age 18 years or older
- ECOG performance status 1 or less (Karnofsky 70% or higher)
- Hemoglobin ≥ 9.0 g/dL within 14 days prior to treatment
- Absolute neutrophil count ≥ 1,500/mcL within 14 days prior to treatment
- Platelets ≥ 100,000/mcL within 14 days prior to treatment
- Total bilirubin ≤ 1.5 times institutional upper limit of normal within 14 days prior to treatment
- AST/ALT ≤ 2.5 times institutional upper limit of normal within 14 days prior to treatment
- Glomerular filtration rate ≥ 60 mL/min/1.73 m² if creatinine elevated within 14 days prior to treatment
- PT/INR and PTT < 1.5 times upper limit of normal within 14 days prior to treatment
- Albumin > 2.5 g/dL within 14 days prior to treatment
- Treated brain metastases allowed if stable without progression for at least 4 weeks
- Prior or concurrent malignancy allowed if not interfering with study assessments
- New York Heart Association Functional Classification class 2B or better
- Ability to swallow and retain oral medication
- Negative pregnancy test within 7 days of starting treatment for women of childbearing potential
- Use of contraception during and for 3 months after study participation for women and their male partners
- Ability to understand and sign informed consent
- Patients with hepatitis C must be treated and cured or have undetectable viral load if on treatment
You will not qualify if you...
- Anti-cancer therapy within 30 days or 5 half-lives before first dose
- Radiation therapy within 21 days before first dose
- Diagnosis of NK cell lymphoma
- Unresolved toxicities from prior therapy greater than grade 1, except alopecia or stable grade 2 not overlapping with study drugs
- Receiving other investigational agents
- Untreated or symptomatic brain or leptomeningeal metastases
- Significant malabsorption or nausea/vomiting interfering with oral therapy
- Bleeding disorders or significant bleeding within prior 6 months
- Allergic reactions to similar drugs to entinostat or ZEN003694
- Use of strong CYP3A4 inhibitors/inducers or CYP1A2 substrates with narrow therapeutic windows
- Uncontrolled intercurrent illness
- Pregnant or breastfeeding women
- Cardiac conditions including QTcF > 450 msec, arrhythmias, pacemaker with paced rhythm, NYHA class ≥ II heart failure, recent acute coronary syndrome or stenting
- Use of oral Factor Xa or Factor IIa inhibitors (low molecular weight heparin allowed)
- Radiation to more than 25% of bone marrow
- Bone-targeted radionuclide therapy within 6 weeks before first dose
- Previous treatment with ZEN003694, HDAC inhibitors, or investigational BET inhibitors
- Major surgery within 4 weeks before first dose except diagnostic, dental, or stenting procedures
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Repeated 28-day cycles until disease progression or discontinuation
Participants receive entinostat orally on days 1, 8, 15, and 22 of each 28-day cycle and ZEN003694 orally on days 1-5, 8-12, 15-19, and 22-26 of each cycle. Cycles repeat every 28 days until disease progression or unacceptable toxicity. Participants undergo core needle biopsy before starting treatment and may have additional core needle biopsies during treatment. Computed tomography scans are performed throughout the study to monitor disease.
Weekly visits during each 28-day cycle; additional visits for biopsies and CT scans
Follow-up
Duration - 30 days
After completing treatment, participants are followed for 30 days to monitor safety and overall health.
1 to 2 visits depending on participant status
Trial Site Locations
Total: 3 locations
1
Yale University
New Haven, Connecticut, United States, 06520
Actively Recruiting
2
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States, 32610
Actively Recruiting
3
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Actively Recruiting
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How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
1
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