- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06357858
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck
Biomarker Driven Phase 1/1b Trial of ASTX727 and Nivolumab in Patients With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck
The goal of this clinical trial is to see if the combination of experimental drug ASTX727 and Nivolumab enhances the antitumor immune response in participants will recurrent or metastatic squamous cell carcinoma of the head and neck.
Participants will take a pill called ASTX727 for 4 or 5 days every month followed by an injection of Nivolumab one week after the first dose of study medication.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Kyunghee Burkitt, DO, PhD
- Phone Number: 216-844-0512
- Email: Kyunghee.Burkitt@UHhospitals.org
Study Locations
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
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Contact:
- Kyunghee Burkitt, DO, PhD
- Phone Number: 216-844-0512
- Email: Kyunghee.Burkitt@UHhospitals.org
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed recurrent or metastatic HNSCC considered incurable by local therapies and eligible to receive anti-PD-L1 as first-line treatment (PD-L1 positive with combined positive score (CPS) ≥1 as evaluated in pre-screening).
- Participants must have primary tumor locations in following; oral cavity, hypopharynx, or larynx (nasopharynx is not allowed).
- Participants must have not received prior therapies for this disease, no systemic therapy administered in the recurrent or metastatic setting (except for systemic therapy completed within 6 months or > 6 months if given as part of multimodal treatment for locally advanced disease).
- Participants must have not received prior treatment with immune checkpoint inhibitors.
- Participants can provide archival tumor tissue not older than 12 months from a core or excisional biopsy for PD-L1 pre-screening using the PD-L1 IHC 22C3 pharmDx assay.
- Participants must have lesions amenable to obtain pre-treatment tumor biopsies in screening period after eligibility confirmation and before start of treatment and on- treatment tumor biopsies on C1D8 & C3D8 after start of treatment if lesions are still present at that time. If a recent archival biopsy is obtained within 3 months prior to start of treatment, this biopsy can be used as a pre-treatment biopsy.
- Participants should be age >18 years.
- Participants should have ECOG Performance status ≤ 2.
- Participants should have ability to swallow pills (participants will have to demonstrate the ability to swallow a placebo during screening).
Participants must have normal organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dl
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Total bilirubin within normal institutional limits (Gilbert's syndrome related elevated bilirubin is accepted as long as levels have been stable within last 3 months).
- AST (SGOT) ≤ 2.5 X institutional upper limit of normal
- ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
- Serum Creatinine within normal institutional limits
- Women of child-bearing potential and sexually active men with female partners of child-bearing potential must agree to use a highly effective method of contraception beginning with the first dose of study therapy and for the duration of their participation in the study. This is expected for the entire duration of the study period through 6 months after the last dose. Highly effective methods of contraception include: female sterilization (tubal ligation, bilateral oophorectomy, and/or hysterectomy); male sterilization (at least 6 months prior to screening); intrauterine device; and oral, injected, or implanted hormonal contraception AND barrier methods of contraception. Women of child-bearing potential must have documented negative pregnancy test prior to start of investigational treatment regimen. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Participants must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Participants with progressive disease within six months of completion of curatively Intended systemic treatment for locoregionally advanced HNSCC.
- Participants with history of severe immune related adverse effects from prior immunotherapy, except hypothyroidism clinically stable on hormone replacement treatment and controlled type 1 diabetes. All other endocrinopathies are excluded even if controlled with medications.
- Participants with Grade ≥ 3 infections within 4 weeks before the first study drug administration. Clinically active infections > Grade 1 within 2 weeks before the first study drug administration.
- Participants with previous or active myocarditis/myositis in history (independent of cause).
- Participants with pneumonitis, idiopathic pulmonary fibrosis, organizing, interstitial lung disease active or history of autoimmune disease. . Autoimmune thyroid disease as well as other non-life threatening autoimmune diseases such as vitiligo or autoimmune alopecia that don't require systemic immunosuppression are not excluded.
- Participants with known human immunodeficiency virus (HIV) infection, uncontrolled active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- Participants with treatment with systemic immunosuppressant medications within 2 weeks before the first study drug administration. However, low-dose steroid use (prednisone equivalent <=10mg daily) for other reasons is allowed.
- Participants receiving any other investigational agents.
- Participants with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Participants with confirmed COVID-19 within 7 days prior to start treatment will be excluded, however upon recovery with confirmation of negative COVID test, participant can be reconsidered for the study.
- Participants with a history of hypersensitivity to active or inactive excipients of ASTX727 or nivolumab or drugs with a similar chemical structure or class to either agent.
- Participants with any other condition which in the Investigator's opinion would not make the participant a good candidate for the clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Oral Decitabine + Nivolumab
Oral decitabine (ASTX727) will be administered during D1-5 (DL1) or D1-4 (DL1-1) followed by Nivolumab on D8 with every 4 week cycle.
The expected minimum treatment cycle is 2 and maximum treatment cycle of 6.
However, treatment can be continued until disease progression.
|
Oral decitabine (ASTX727) will be administered during D1-5 (DL1) or D1-4 (DL1-1).
Other Names:
Nivolumab will be administered on D8 with every 4 week cycle.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacodynamics Effect of ASTX727 on global DNA methylation status
Time Frame: 12 months after completion of treatment
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To find a biologically effective dose of ASTX727 in this clinical trial, levels of global DNA methylation at pre- versus post-ASTX727 will be compared using Wilcoxon signed-rank test.
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12 months after completion of treatment
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Immunogenicity of ASTX27 in combination with Nivolumab
Time Frame: 12 months after completion of treatment
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To investigate the whether DNA methylation status affect immunologic biomarkers, changes in methylation status at pre-, post-ASTX727 and on treatment of ASTX727 plus Nivolumab will be correlated with the changes in immunologic biomarkers.
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12 months after completion of treatment
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Maximum Tolerated Dose
Time Frame: 12 months after completion of treatment
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Establish the maximum tolerated dose (MTD) in Phase I part 1.
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12 months after completion of treatment
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Safety of ASTX
Time Frame: 12 months after completion of treatment
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Assess safety of ASTX in combination with Nivolumab.
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12 months after completion of treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: 12 months after completion of treatment
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The true objective response rate will be estimated based on the number of responses using a binomial distribution and its confidence interval will be estimated using Wilson's method.
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12 months after completion of treatment
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Overall Survival (OS)
Time Frame: 12 months after completion of treatment
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Overall survival will be measured from the date of enrollment to the date of death.
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12 months after completion of treatment
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Kyunghee Burkitt, DO, PhD, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Head and Neck Neoplasms
- Neoplasms, Squamous Cell
- Carcinoma
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Decitabine
- Nivolumab
- Decitabine and cedazuridine drug combination
Other Study ID Numbers
- CASE6323
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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