Window Trial 5-aza in HNSCC, T-tare

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.

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Key information

Conditions

Head and Neck Squamous Cell Carcinoma Carcinoma Carcinoma, Squamous Cell Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Squamous Cell Carcinoma of Head and Neck

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Smilow Cancer Center at Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

5-Azacitadine

Drug

Other names: Vidaza

Primary outcomes

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.

Sponsors and collaborators

Lead sponsor

Yale University

Other

Registry information

Official study 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

Important dates

Study start: 2015
Primary completion: 2019
Study completion: 2019
First posted: Jun 30, 2014
Registry last updated: Feb 15, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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