Window Trial 5-aza in HNSCC, T-tare

Yale University

Status and phase: Completed; Phase 1

Conditions: Head and Neck Squamous Cell Carcinoma

Treatments: Drug: 5-Azacitadine

Study type: Interventional

Funder types: Other

Identifiers

NCT02178072

1404013771

Details and patient eligibility

About

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.

Full 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

Enrollment: 18 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

18 participants in 2 patient groups

HPV positive

Other group

Description:

HPV positive patients

Treatment:

Drug: 5-Azacitadine

HPV negative

Other group

Description:

HPV negative patients

Treatment:

Drug: 5-Azacitadine