Head and Neck Squamous Cell CarcinomaPhase 1NCT02178072
Window Trial 5-aza in HNSCC, T-tare
A Phase 1 study testing 5-Azacitadine in people with Head and Neck Squamous Cell Carcinoma, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to assess the activity of 5-azacitidine in patients with Human Papilloma Virus (HPV)-positive and HPV- negative head and neck squamous cell carcinoma (HNSCC). The response activity will be determined by analyzing your tumor tissue prior to and after treatment with 5-azacitidine. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- 5-Azacitadine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Feb 2015to 23 Oct 2019
- 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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed p16 or HPV PCR positive HNSCC with surgically resectable disease
- Age ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
- ANC greater than or equal to 1500, Hb greater than or equal to 8, platelet count greater than or equal to 100,000
Who cannot join
- AST or ALT greater than 2.5 x ULN
- Known brain metastases
- Women must not be pregnant or breastfeeding
- Known allergy to 5-azacitadine
- Patients receiving any other investigational agents within 4 weeks of starting the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Smilow Cancer Center at Yale New Haven Hospital
New Haven, Connecticut, 06510
About this study
Official title: A Window Study to Assess the Activity of Demethylation Therapy in Patients With HPV-Positive Compared With HPV-Negative Head and Neck Squamous Cell Carcinoma, With Response Assessment and Biomarker Expansion Cohort in HPV-Positive Oropharynx Cancer
The purpose of this study is to assess the activity of 5-azacitidine in patients with Human Papilloma Virus (HPV)-positive and HPV- negative head and neck squamous cell carcinoma (HNSCC). The response activity will be determined by analyzing your tumor tissue prior to and after treatment with 5-azacitidine. Preliminary studies in mice bearing human head and neck cancers or head and neck cancer cells cultured in laboratories suggest that treatment with 5-azacitidine increases changes in cancer cells that lead to their death. This study is designed to determine if similar changes occur in cancer cells of patients with head and neck cancer.
The study also aims to determine the amount of a specific type of protein, p53 before and after treatment. Research has shown that the p53 protein is associated with anti-tumor activity.
Finally, this study is measuring the amount of a specific type of protein called interferon in your tumor tissue. Interferons are proteins made and released by the body in response to pathogens (disease causing agents) such as viruses, bacteria, or tumor cells. Interferons allow for communication between cells to trigger the protective defenses of the immune system that remove pathogens (disease causing agents) or tumors.
Read the detailed description
Primary Objectives:
The primary objectives of this study are:
- to determine the proportion of HPV-positive patients in whom 5-azacytidine increases APOBEC RNA expression.
Secondary Objectives
The secondary objectives of this study are:
- to investigate response (proliferation, apoptosis), as well as reactivation of IFN pathways in patients treated with 5-azacitadine for HPV-positive and HPV-negative HNSCC.
- to investigate the clinical activity of 5-azacitadine in patients with HPV-positive and HPV-negative HNSCC.
- to investigate the safety of 5-azacitadine in patients with HPV-positive and HPV-negative HNSCC
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- 5-Azacitadine
- Keywords
- HNSCC
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-AzacitadineDrug
Also called Vidaza
| Study group | Role | What they receive |
|---|---|---|
| HPV positive | Other | HPV positive patients Receives: Drug: 5-Azacitadine |
| HPV negative | Other | HPV negative patients Receives: Drug: 5-Azacitadine |
What is being measured
The primary outcome is the main question the study is designed to answer.
tumor response
The post-treatment biopsy will occur the day after the last injection of 5-azacytidine. 5-aza is currently FDA-approved and used for therapy of myelodysplastic syndrome. Pre- and post- 5-aza treatment tissue will be analyzed for proliferation (IHC-Ki-67), apoptosis (IHC-cleaved caspase-3, cleaved PARP-1), and for p53 protein (IHC, immunoblots), as well as p53, CDKN1A, MDM2, IFITs, and CCL5 mRNA levels (as described above). The primary outcome is the change from baseline of the p53 protein level in post-treatment vs. pre-treatment biopsies. Although tumor response may not be expected due to the short treatment course, the post-treatment vs. pre-treatment change from baseline of the gross tumor measurements will be used to measure tumor response.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2014 (estimated)
- Study start19 Feb 2015
- Primary completion23 Oct 2019
- Study completion23 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Barbara Burtness, MD, Principal investigator, Yale University School of Medicine, Smilow Cancer Center at Yale New Haven Hospital, Yale Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02178072
- Sponsor's protocol ID
- 1404013771
- Status last verified
- Feb 2022
- First submitted
- 23 Jun 2014
- Last updated
- 15 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Window Study to Assess the Activity of Demethylation Therapy in Patients With HPV-Positive Compared With HPV-Negative Head and Neck Squamous Cell Carcinoma, With Response Assessment and Biomarker Expansion Cohort in HPV-Positive Oropharynx Cancer
- ClinicalTrials.gov ID
- NCT02178072
- Acronym / sponsor ID
- 1404013771
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Keywords
- HNSCC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 19 Feb 2015 (actual)
- Primary completion
- 23 Oct 2019 (actual)
- Study completion
- 23 Oct 2019 (actual)
- First posted
- 30 Jun 2014 (estimated)
- 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 purpose of this study is to assess the activity of 5-azacitidine in patients with Human Papilloma Virus (HPV)-positive and HPV- negative head and neck squamous cell carcinoma (HNSCC). The response activity will be determined by analyzing your tumor tissue prior to and after treatment with 5-azacitidine. Preliminary studies in mice bearing human head and neck cancers or head and neck cancer cells cultured in laboratories suggest that treatment with 5-azacitidine increases changes in cancer cells that lead to their death. This study is designed to determine if similar changes occur in cancer cells of patients with head and neck cancer.
The study also aims to determine the amount of a specific type of protein, p53 before and after treatment. Research has shown that the p53 protein is associated with anti-tumor activity.
Finally, this study is measuring the amount of a specific type of protein called interferon in your tumor tissue. Interferons are proteins made and released by the body in response to pathogens (disease causing agents) such as viruses, bacteria, or tumor cells. Interferons allow for communication between cells to trigger the protective defenses of the immune system that remove pathogens (disease causing agents) or tumors.
Detailed description
Primary Objectives:
The primary objectives of this study are:
- to determine the proportion of HPV-positive patients in whom 5-azacytidine increases APOBEC RNA expression.
Secondary Objectives
The secondary objectives of this study are:
- to investigate response (proliferation, apoptosis), as well as reactivation of IFN pathways in patients treated with 5-azacitadine for HPV-positive and HPV-negative HNSCC.
- to investigate the clinical activity of 5-azacitadine in patients with HPV-positive and HPV-negative HNSCC.
- to investigate the safety of 5-azacitadine in patients with HPV-positive and HPV-negative HNSCC
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HPV positive | Other | Drug: 5-AzacitadineHPV positive patients |
| HPV negative | Other | Drug: 5-AzacitadineHPV negative patients |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed p16 or HPV PCR positive HNSCC with surgically resectable disease
- Age ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
- ANC greater than or equal to 1500, Hb greater than or equal to 8, platelet count greater than or equal to 100,000
Key exclusion criteria (5 listed)
- AST or ALT greater than 2.5 x ULN
- Known brain metastases
- Women must not be pregnant or breastfeeding
- Known allergy to 5-azacitadine
- Patients receiving any other investigational agents within 4 weeks of starting the study
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 |
|---|---|---|
| 5-AzacitadineAlso: Vidaza | Drug | HPV negative, HPV positive |
Primary outcome
tumor response
Time frame: 6 months
The post-treatment biopsy will occur the day after the last injection of 5-azacytidine. 5-aza is currently FDA-approved and used for therapy of myelodysplastic syndrome. Pre- and post- 5-aza treatment tissue will be analyzed for proliferation (IHC-Ki-67), apoptosis (IHC-cleaved caspase-3, cleaved PARP-1), and for p53 protein (IHC, immunoblots), as well as p53, CDKN1A, MDM2, IFITs, and CCL5 mRNA levels (as described above). The primary outcome is the change from baseline of the p53 protein level in post-treatment vs. pre-treatment biopsies. Although tumor response may not be expected due to the short treatment course, the post-treatment vs. pre-treatment change from baseline of the gross tumor measurements will be used to measure tumor response.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2022.
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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.
Barbara Burtness, MD principal investigator
Yale University School of Medicine, Smilow Cancer Center at Yale New Haven Hospital, Yale 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 5-Azacitadine in people with Head and Neck Squamous Cell Carcinoma, run by Yale University 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 4 inclusion and 5 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: finished, as of the sponsor's last update on 15 Feb 2022. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
tumor response (time frame: 6 months). 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 15 Feb 2022.