Clinical trial NCT01695122: Valproic Acid and Platinum-based Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma
Official title: Efficacy Evaluation of the Combination of Valproic Acid and Standard Platinum-based Chemoradiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Oral Cavity Cancer
Oropharyngeal Cancer
Keywords: Head and Neck Cancer
Oropharyngeal cancer
Oral cavity cancer
Chemoradiation
valproic acid
histone deacetylase
Lead sponsor: Instituto do Cancer do Estado de São Paulo
Sponsor class: OTHER
Collaborators: name: University of Sao Paulo
First posted: 2012-09-27
Enrollment: 14
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Response Rate
timeFrame: Within 6 to 8 weeks after completion of chemoradiation
Secondary outcomes:
measure: Adverse reactions to study treatment
measure: Progression free survival
timeFrame: Three years
measure: Overall survival
timeFrame: Three Years
measure: Response rate comparison by p16 status
measure: Quality of life
Other outcomes:
measure: Biomarkers assessment
Locations:
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo
state: SP
Study officials:
affiliation: Instituto do Cancer do Estado de Sao Paulo - University of Sao Paulo
name: Milena P Mak, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mak MP, Pasini FS, Diao L, Garcia FOT, Takahashi TK, Nakazato D, Martins RE, Almeida CM, Kulcsar MAV, Lamounier VA, Nunes EM, de Souza IC, Garcia MRT, Amadio AV, Siqueira SAC, Snitcovsky IML, Sichero L, Wang J, de Castro G Jr. Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers. Ecancermedicalscience. 2020 Dec 15;14:1155. doi: 10.3332/ecancer.2020.1155. eCollection 2020.