Valproic Acid and Platinum-based Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma
Primary Purpose
Head and Neck Cancer, Oral Cavity Cancer, Oropharyngeal Cancer
Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Valproic Acid
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer focused on measuring Head and Neck Cancer, Oropharyngeal cancer, Oral cavity cancer, Chemoradiation, valproic acid, histone deacetylase
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
Sites / Locations
- Instituto do Cancer do Estado de Sao Paulo
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
valproic acid
Arm Description
Outcomes
Primary Outcome Measures
Response Rate
RECIST v 1.1
Secondary Outcome Measures
Adverse reactions to study treatment
Progression free survival
Overall survival
Response rate comparison by p16 status
Quality of life
Full Information
NCT ID
NCT01695122
First Posted
September 25, 2012
Last Updated
February 22, 2016
Sponsor
Instituto do Cancer do Estado de São Paulo
Collaborators
University of Sao Paulo
1. Study Identification
Unique Protocol Identification Number
NCT01695122
Brief Title
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
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto do Cancer do Estado de São Paulo
Collaborators
University of Sao Paulo
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer, Oral Cavity Cancer, Oropharyngeal Cancer
Keywords
Head and Neck Cancer, Oropharyngeal cancer, Oral cavity cancer, Chemoradiation, valproic acid, histone deacetylase
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
valproic acid
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Valproic Acid
Other Intervention Name(s)
sodium valproate
Primary Outcome Measure Information:
Title
Response Rate
Description
RECIST v 1.1
Time Frame
Within 6 to 8 weeks after completion of chemoradiation
Secondary Outcome Measure Information:
Title
Adverse reactions to study treatment
Title
Progression free survival
Time Frame
Three years
Title
Overall survival
Time Frame
Three Years
Title
Response rate comparison by p16 status
Title
Quality of life
Other Pre-specified Outcome Measures:
Title
Biomarkers assessment
10. Eligibility
Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Milena P Mak, MD
Organizational Affiliation
Instituto do Cancer do Estado de Sao Paulo - University of Sao Paulo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto do Cancer do Estado de Sao Paulo
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05409-011
Country
Brazil
12. IPD Sharing Statement
Citations:
PubMed Identifier
33574900
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.
Results Reference
derived
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Valproic Acid and Platinum-based Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma
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