Recurrent Squamous Cell Carcinoma of the Head and NeckPhase 1NCT06357858
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck
A Phase 1 study testing INQOVI (decitabine and cedazuridine) and Nivolumab in people with Recurrent Squamous Cell Carcinoma of the Head and Neck and Metastatic Squamous Cell Carcinoma, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Recurrent Squamous Cell Carcinoma of the Head and Neck, Metastatic Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- INQOVI (decitabine and cedazuridine) and Nivolumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2024to 28 Feb 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
About this study
Official title: 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.
Read the detailed description
Anti PD1 inhibitor (Pembrolizumab, Nivolumab) is approved for recurrent/metastatic HNCC. However, response rates to Pembrolizumab or Nivolumab monotherapy are as low as 16-19%, underscoring the presence of immune evasion mechanisms. One of the main immune escape mechanisms described in HNSCC is poor tumor microenvironment characterized by defective HLA class I processing and antigen presentation, which allows tumor cells to evade their detection and destruction by cytotoxic CD8+ T-cells. Mutations or downregulation of the expression of HLA class I component including beta-2- microglobulin (β2M) and antigen processing machinery (APM) genes have been correlated with poor prognosis of HNSCC. Recent studies showed that de novo DNA methylation programs renders terminal T cell exhaustion and subsequent exhausted T cells are refractory to PD-1 blockade mediated rejuvenation. Pretreatment with DNA methyltransferases (DNMT) inhibitor prior to PD-L1 blockade showed enhancement of T cell responses and tumor control during PD-1 inhibitors in mice. A pilot study of novel combination of antiPD-1 and decitabine was conducted in patients with refractory or recurrent AML. The showed a best response of stable disease or better in 6 of 10 patients in patients with R-AML. A phase II clinical trial of anti-PD-1 camrelizumab plus decitabine, in relapsed/refractory Hodgkin lymphoma showed CR rate of 79% with decitabine plus camrelizumab compared to 32% with camrelizumab alone. Based on the promising results of decitabine enhances immune response and antitumor activity shown in both preclinical and preliminary clinical data from the phase II trial of hematological malignancies, I hypothesize that ASTX727 (oral decitabine and cedazuridine) changes DNA methylation status which may enhance the antitumor immune response by modulating tumor immune microenvironment and promoting increased tumor-infiltrating lymphocytes, which may enhance response to anti-PD1 inhibitor in R/M HNSCC patients
- Conditions
- Recurrent Squamous Cell Carcinoma of the Head and Neck, Metastatic Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma
- Being tested
- INQOVI (decitabine and cedazuridine), Nivolumab
- Keywords
- ASTX727, Nivolumab
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INQOVI (decitabine and cedazuridine)Drug
Also called ASTX727
Oral decitabine (ASTX727) will be administered during D1-5 (DL1) or D1-4 (DL1-1).
NivolumabDrug
Also called OPDIVO
Nivolumab will be administered on D8 with every 4 week cycle.
| Study group | Role | What they receive |
|---|---|---|
| Oral Decitabine + Nivolumab | Experimental | 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. Receives: Drug: INQOVI (decitabine and cedazuridine); Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacodynamics Effect of ASTX727 on global DNA methylation status
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.
Measured: 12 months after completion of treatment
Immunogenicity of ASTX27 in combination with Nivolumab
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.
Measured: 12 months after completion of treatment
Maximum Tolerated Dose
Establish the maximum tolerated dose (MTD) in Phase I part 1.
Measured: 12 months after completion of treatment
Safety of ASTX
Assess safety of ASTX in combination with Nivolumab.
Measured: 12 months after completion of treatment
Secondary outcomes (2)
Objective Response Rate (ORR)
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.
Measured: 12 months after completion of treatment
Overall Survival (OS)
Overall survival will be measured from the date of enrollment to the date of death.
Measured: 12 months after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2024
- Study start1 Jun 2024 (estimated)
- Primary completion28 Feb 2025 (estimated)
- Study completion28 Feb 2026 (estimated)
Why it stopped: Funding unavailable
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kyunghee Burkitt, DO, PhD, Principal investigator, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06357858
- Sponsor's protocol ID
- CASE6323
- Status last verified
- Jul 2024
- First submitted
- 5 Apr 2024
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker Driven Phase 1/1b Trial of ASTX727 and Nivolumab in Patients With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck
- ClinicalTrials.gov ID
- NCT06357858
- Acronym / sponsor ID
- CASE6323
- Conditions
- Recurrent Squamous Cell Carcinoma of the Head and Neck, Metastatic Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma
- Keywords
- ASTX727, Nivolumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding unavailable
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 Jun 2024 (estimated)
- Primary completion
- 28 Feb 2025 (estimated)
- Study completion
- 28 Feb 2026 (estimated)
- First posted
- 10 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Anti PD1 inhibitor (Pembrolizumab, Nivolumab) is approved for recurrent/metastatic HNCC. However, response rates to Pembrolizumab or Nivolumab monotherapy are as low as 16-19%, underscoring the presence of immune evasion mechanisms. One of the main immune escape mechanisms described in HNSCC is poor tumor microenvironment characterized by defective HLA class I processing and antigen presentation, which allows tumor cells to evade their detection and destruction by cytotoxic CD8+ T-cells. Mutations or downregulation of the expression of HLA class I component including beta-2- microglobulin (β2M) and antigen processing machinery (APM) genes have been correlated with poor prognosis of HNSCC. Recent studies showed that de novo DNA methylation programs renders terminal T cell exhaustion and subsequent exhausted T cells are refractory to PD-1 blockade mediated rejuvenation. Pretreatment with DNA methyltransferases (DNMT) inhibitor prior to PD-L1 blockade showed enhancement of T cell responses and tumor control during PD-1 inhibitors in mice. A pilot study of novel combination of antiPD-1 and decitabine was conducted in patients with refractory or recurrent AML. The showed a best response of stable disease or better in 6 of 10 patients in patients with R-AML. A phase II clinical trial of anti-PD-1 camrelizumab plus decitabine, in relapsed/refractory Hodgkin lymphoma showed CR rate of 79% with decitabine plus camrelizumab compared to 32% with camrelizumab alone. Based on the promising results of decitabine enhances immune response and antitumor activity shown in both preclinical and preliminary clinical data from the phase II trial of hematological malignancies, I hypothesize that ASTX727 (oral decitabine and cedazuridine) changes DNA methylation status which may enhance the antitumor immune response by modulating tumor immune microenvironment and promoting increased tumor-infiltrating lymphocytes, which may enhance response to anti-PD1 inhibitor in R/M HNSCC patients
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral Decitabine + Nivolumab | Experimental | Drug: INQOVI (decitabine and cedazuridine), Drug: NivolumabOral 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INQOVI (decitabine and cedazuridine)Also: ASTX727Oral decitabine (ASTX727) will be administered during D1-5 (DL1) or D1-4 (DL1-1). | Drug | Oral Decitabine + Nivolumab |
| NivolumabAlso: OPDIVONivolumab will be administered on D8 with every 4 week cycle. | Drug | Oral Decitabine + Nivolumab |
Primary outcome
Pharmacodynamics Effect of ASTX727 on global DNA methylation status
Time frame: 12 months after completion of treatment
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.
Immunogenicity of ASTX27 in combination with Nivolumab
Time frame: 12 months after completion of treatment
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.
Maximum Tolerated Dose
Time frame: 12 months after completion of treatment
Establish the maximum tolerated dose (MTD) in Phase I part 1.
Safety of ASTX
Time frame: 12 months after completion of treatment
Assess safety of ASTX in combination with Nivolumab.
2 secondary outcomes
Objective Response Rate (ORR)
Time frame: 12 months after completion of treatment
Overall Survival (OS)
Time frame: 12 months after completion of treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kyunghee Burkitt, DO, PhD principal investigator
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INQOVI (decitabine and cedazuridine) and Nivolumab in people with Recurrent Squamous Cell Carcinoma of the Head and Neck and Metastatic Squamous Cell Carcinoma, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacodynamics Effect of ASTX727 on global DNA methylation status (time frame: 12 months after completion of treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.