Window Trial 5-aza in HNSCC, T-tare

NCT02178072 | Completed Phase 1 DMC

• 1 other identifier: 1404013771
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

HNSCC

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

HPV positive

OTHER

HPV positive patients

Drug: 5-Azacitadine

HPV negative

OTHER

HPV negative patients

Drug: 5-Azacitadine

Interventions

5-Azacitadine DRUG

Also known as: Vidaza

HPV negative; HPV positive

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Smilow Cancer Center at Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Barbara Burtness, MD

  Yale University School of Medicine, Smilow Cancer Center at Yale New Haven Hospital, Yale Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2014
• First Posted: June 30, 2014
• Study Start: February 19, 2015
• Primary Completion: October 23, 2019
• Study Completion: October 23, 2019
• Last Updated: February 15, 2022

Record last verified: 2022-02

Locations

US (1)