Clinical trial NCT02178072: Window Trial 5-aza in HNSCC, T-tare
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: HNSCC
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2014-06-30
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed p16 or HPV PCR positive HNSCC with surgically resectable disease
2. Age ≥18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
4. 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:

1. AST or ALT greater than 2.5 x ULN
2. Known brain metastases
3. Women must not be pregnant or breastfeeding
4. Known allergy to 5-azacitadine
5. Patients receiving any other investigational agents within 4 weeks of starting the study

Primary outcomes:
measure: tumor response
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Smilow Cancer Center at Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University School of Medicine, Smilow Cancer Center at Yale New Haven Hospital, Yale Comprehensive Cancer Center
name: Barbara Burtness, MD
role: PRINCIPAL_INVESTIGATOR
References: