Window Trial 5-aza in HNSCC, T-tare | NCT02178072

Studies
Window Trial 5-aza in HNSCC, T-tare

NCT02178072

Sponsor

Yale University

Status

Completed

Last Update Posted

Feb 15, 2022Actual

Enrollment

18Actual

Phase

Phase 1

Conditions

Head and Neck Squamous Cell Carcinoma

Interventions

5-Azacitadine

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

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

Status Module

Record Verification Date

Feb 2022

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Feb 19, 2015Actual

Primary Completion Date

Oct 23, 2019Actual

Completion Date

Oct 23, 2019Actual

First Submitted Date

Jun 23, 2014

First Submission Date that Met QC Criteria

Jun 26, 2014

First Posted Date

Jun 30, 2014Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Feb 3, 2022

Last Update Posted Date

Feb 15, 2022Actual

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief 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. 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

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

18Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
HPV positive	Other	HPV positive patients	Drug: 5-Azacitadine
HPV negative	Other	HPV negative patients	Drug: 5-Azacitadine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
5-Azacitadine	Drug		HPV negative HPV positive	Vidaza

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	6 months

Secondary Outcomes

Not provided

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

99 Years

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Barbara Burtness, MD	Yale University School of Medicine, Smilow Cancer Center at Yale New Haven Hospital, Yale Comprehensive Cancer Center	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Smilow Cancer Center at Yale New Haven Hospital		New Haven	Connecticut	06510	United States

Condition Browse Module

MeSH Terms

ID	Term
D000077195	Squamous Cell Carcinoma of Head and Neck

Ancestor Terms

ID	Term
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

Browse Leaves

Not provided

Browse Branches

Not provided

Intervention Browse Module

MeSH Terms

ID	Term
D001374	Azacitidine

Ancestor Terms

ID	Term
D001372	Aza Compounds
D009930	Organic Chemicals
D003562	Cytidine
D011741	Pyrimidine Nucleosides

Browse Leaves

Not provided

Browse Branches

Not provided