Chemoprevention of Head and Neck Squamous Cell Carcinoma (HNSCC) With Valproic Acid (GAMA)
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|ClinicalTrials.gov Identifier: NCT02608736|
Recruitment Status : Completed
First Posted : November 20, 2015
Last Update Posted : February 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Squamous Cell Carcinoma||Drug: Valproic Acid Drug: Placebo||Early Phase 1|
Chemoprevention is an attractive strategy to reduce the incidence of squamous cell carcinoma of the head and neck, although past trials have not demonstrated its feasibility.
Valproic acid (VA) is a modifier of epigenetic events as it is an histone deacetylase inhibitor and causes DNMT degradation. The histone deacetylase inhibitors (e.g. VA) encompasses a new class of anti-tumor drugs, that can affect multiple pathways related to tumor initiation and progression due to histone and non-histone protein acetylation and DNMT degradation. VA promote histone acetylation when orally administered with a dose of 20-40 mg/kg, per day or 1000/1500 mg, per day.
Initially the authors will study saliva from participants documenting if there is saliva histone acetylation and if a difference in DNMT expression in saliva exists when comparing valproic acid arm to placebo arm (biological validation) after giving placebo or valproic acid for three months.
This will be the initial step of a bigger project. If authors prove that there will be a difference in histone acetylation and/or DNMT expression between groups they will launch a randomized, double blind, placebo control clinical trial (phase 3 clinical trial), to evaluate VA action as a chemopreventive agent in HNSCC patients who usually carries a high chance to develop recurrence (stages III/IV) or second primary malignancies (stages I/II/III/IV).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Phase 0 Clinical Trial With Valproic Acid as a Chemopreventive Agent in Patients With Head and Neck Squamous Cell Carcinoma Previously Treated|
|Study Start Date :||December 2015|
|Actual Primary Completion Date :||December 2016|
|Actual Study Completion Date :||July 2017|
Experimental: Valproic Acid
Valproic acid will be orally administered in a total dose of 1500mg per day (500mg, every 8 hours), for three months.
Drug: Valproic Acid
Half of the participants will receive valproic acid orally for three months. Saliva and blood will be sampled in the study entry. The participants will be followed with blood tests every month for three cycles. After the third cycle, saliva and blood will be sampled once more. Finally, histone acetylation and DNMT expression will be studied comparing the samples collected in different timelines and comparing them to saliva collected in placebo arm.
Placebo Comparator: Placebo
Placebo will be orally administered in a total dose of three capsules per day (every 8 hours), for three months.
The other half of the participants will receive placebo for three months. Saliva and blood will be sampled in the study entry. The participants will be followed with blood tests every month for three cycles. After the third cycle, saliva and blood will be sampled once more. Finally, histone acetylation and DNMT expression will be studied comparing the samples collected in different timelines and comparing them to saliva collected in valproic acid arm.
Other Name: Inert, not active
- Changes in protein or histone acetylation [ Time Frame: Three months after study enrollment ]Saliva samples will be collected in baseline and three months after study enrolment. Histone acetylation will be quantified (through ELISA method) and compared in the same arm (if there will be a change in histone acetylation when looking at these different timelines) and between arms (if one group will have or will not have more histone acetylation than the other).
- Incidence of Treatment-Emergent Adverse Events [ Time Frame: Day 1 of each new cycle up to 3 months (3 months of treatment and 3 months of follow-up), in other words, from day 1 of the first cycle until the date of first documented emergent adverse event, assessed up to 6 months ]Evaluation of incidence of treatment-induced adverse events at the beginning of each new cycle (day 1, every 30 days, for a total of six months) using Common Toxicity Criteria for Adverse Effects (CTCAE v.4.0).
- Change in DNA methyltransferases expression. (DNMT) [ Time Frame: Three months after study enrollment ]Saliva samples will be collected in baseline and three months after study enrolment. DNA methyltransferases expression (through microarray method) will be compared in the same arm (if there will be a change in DNMT expression when looking at these different timelines) and between arms (if one group will have or will not have a different DNMT expression when compared to the other).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02608736
|Barretos Cancer Hospital|
|Barretos, São Paulo, Brazil, 14784-400|
|Principal Investigator:||Ricardo Gama, MD, PHD||Barretos Cancer Hospital|
|Study Director:||André Lopes Carvalho, MD, PHD||Barretos Cancer Hospital|
|Study Chair:||Luciano de Souza Viana, MD, PHD||Barretos Cancer Hospital|