Valproic Acid and Platinum-based Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if the addition of valproic acid to standard platinum-based chemoradiation as definitive treatment of locally advanced Head and Neck squamous cell carcinoma can improve treatment outcomes, such as response rate.

Detailed Description
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Valproic acid is a known histone deacetylase inhibitor. In addition to activating apoptosis pathways, cell differentiation and downregulating expression of growth factors, it also promotes radiosensitization. Most patients with Head and Neck squamous cell carcinoma are diagnosed with locally advanced disease, in which long term disease control is still a challenge. The incorporation of epigenetic regulation into standard treatment could improve results of definitive platinum-based chemoradiation in such patients.

Official Title
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Efficacy Evaluation of the Combination of Valproic Acid and Standard Platinum-based Chemoradiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Cancer, Oral Cavity Cancer, Oropharyngeal Cancer

Intervention / Treatment
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* Drug: Valproic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable Oropharyngeal or oral cavity squamous cell carcinoma Candidate for definitive chemoradiation No previous treatment Measurable disease according to RECIST v 1.1 Previous neoplasia, other than Head and Neck, with more than five years without evidence of disease; basocellular carcinoma of the skin and in situ cervical dysplasia if resected Age under 60 years ECOG performance status 0-2 Ability of understanding and giving informed consent Adequate renal and hepatic function Adequate bone marrow function Normal serum magnesium Absence of QTc prolongation Life expectancy of over 12 weeks Exclusion Criteria: Pregnancy Distant metastasis Hypersensibility to valproic acid or other antiepileptic drugs Valproic acid chronic use Severe neurologic impairment Uncontrolled comorbidity Hypoalbuminemia Known history of hepatitis B, C or HIV

Ages Eligible for Study
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Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: valproic acid<br> | Drug: Valproic Acid<br> <br> * Other names: sodium valproate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | RECIST v 1.1 | Within 6 to 8 weeks after completion of chemoradiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse reactions to study treatment |  |  | 
| Progression free survival |  | Three years | 
| Overall survival |  | Three Years | 
| Response rate comparison by p16 status |  |  | 
| Quality of life |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, Oropharyngeal cancer, Oral cavity cancer, Chemoradiation, valproic acid, histone deacetylase