Aspirin Mouthwash in Treating Patients With Oral Leukoplakia

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01238185
First received: November 9, 2010
Last updated: August 9, 2013
Last verified: November 2010
  Purpose

RATIONALE: Aspirin mouthwash may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of aspirin mouthwash in treating patients with oral leukoplakia.


Condition Intervention Phase
Precancerous Condition
Drug: acetylsalicylic acid
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Other: questionnaire administration
Procedure: biopsy
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Oral Topical Cyclooxygenase Inhibitor (Aspirin) Mouthwash for Treatment of Oral Dysplasia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • PGE2 levels as assessed by enzyme immunosorbent assay [ Designated as safety issue: No ]
  • COX-1 and COX-2 mRNA as assessed by qRT-PCR [ Designated as safety issue: No ]
  • COX-1 and COX-2 protein expression as assessed by immunohistochemistry and quantified by immunoblotting to determine whether COX inhibition in oral dysplasia tissues is actually possible by use of the mouthwash formulation [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of WHO histological grade and clinical size of dysplastic lesions before and after treatment and assessment of proliferating cell nuclear antigen [ Designated as safety issue: No ]
  • Tolerability and possible oral and other adverse effects using a questionnaire [ Designated as safety issue: Yes ]
  • VEGF mRNA expression as assessed by qRT-PCR [ Designated as safety issue: No ]
  • Protein expression as assessed by ELISA and immunohistochemistry for VEGFA [ Designated as safety issue: No ]
  • Global gene response of dysplastic tissue as assessed by Affymetrix gene expression microarrays [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: February 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • To determine if oral topical acetylsalicylic acid mouthwash achieves modulation of COX-1, COX-2, and prostaglandin in oral dysplasia tissues in patients with oral leukoplakia.
  • To determine if this drug achieves alteration of histopathology and gene and protein expression in tissue.
  • To determine if this drug achieves aspirin-induced tissue changes relating to altered tumor biology.
  • To assess local and general tolerability and safety of this drug in these patients.

OUTLINE: All patients undergo tissue biopsy for histological diagnosis. Patients without a histological diagnosis of precancerous oral dysplasia undergo routine follow-up. Patients with a histological diagnosis of precancerous oral dysplasia are sequentially allocated to 1 of 4 treatment groups.

  • Group 1: Patients receive acetylsalicylic acid mouthwash (one 75 mg tablet dissolved in 250 mL of water) twice daily for 4-6 weeks, gargling for 60 seconds then expectorate it fully, before planned definitive surgical excision.
  • Group 2: Patients receive acetylsalicylic acid mouthwash (two 75 mg tablets of acetylsalicylic acid dissolved in 250 mL of water) twice daily for 4-6 weeks, gargling for 60 seconds then expectorate it fully, before planned definitive surgical excision.
  • Group 3: Patients receive acetylsalicylic acid mouthwash (one 300 mg tablet of acetylsalicylic acid dissolved in 250 mL of water) twice daily for 4-6 weeks, gargling for 60 seconds then expectorate it fully, before planned definitive surgical excision.
  • Group 4: Patients receive acetylsalicylic acid mouthwash (one 300 mg tablet of acetylsalicylic acid dissolved in 250 mL of water) three times daily for 4-6 weeks, gargling for 60 seconds then expectorate it fully, before planned definitive surgical excision.

At the time of definitive surgical excision, the patient is asked to gargle with the last dose of acetylsalicylic acid mouthwash just before being anesthetized. A small biopsy of the dysplasia lesion is taken and examined for immediate effects of the acetylsalicylic acid mouthwash on the dysplasia lesion. The surgically excised tissue is treated in the same way as the initial biopsy tissue (i.e., half being used for routine histology to confirm the diagnosis and the other half for research purposes). Tissue samples are analyzed via enzyme immunosorbent assay, qRT-PCR, immunoblotting, ELISA, immunohistochemistry, gene array analysis, and microvessel density analysis.

Patients complete a questionnaire assessing local and general tolerability as well as adverse effects during the period of use of the mouthwash.

After completion of study treatment, patients are followed periodically.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Clinically diagnosed oral leukoplakia requiring a tissue biopsy for histological diagnosis
  • Attending the outpatient clinic

PATIENT CHARACTERISTICS:

  • Not nursing
  • No known or suspected sensitivity to aspirin or other nonsteroidal anti-inflammatory drugs
  • No diagnosis of asthma or angioedema
  • No contraindications, including any of the following:

    • Active peptic ulceration or a history of peptic ulceration
    • Hemophilia or a history of bleeding disorders
    • Gout or a history of gout

PRIOR CONCURRENT THERAPY:

  • No concurrent regular use of aspirin for heart disease or other reasons
  • No other concurrent nonsteroidal anti-inflammatory drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01238185

Locations
United Kingdom
University of Birmingham
Birmingham, England, United Kingdom, B15 2TT
Institute of Head and Neck Studies and Education
Coventry, England, United Kingdom, CV2 2DX
Sponsors and Collaborators
Institute of Head and Neck Studies and Education, United Kingdom
Investigators
Principal Investigator: Hisham Mehanna, MD Institute of Head and Neck Studies and Education, United Kingdom
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01238185     History of Changes
Other Study ID Numbers: INHANSE-ASPOD, CDR0000688122, ISRCTN31503555, EU-21083
Study First Received: November 9, 2010
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
oral leukoplakia

Additional relevant MeSH terms:
Precancerous Conditions
Neoplasms
Aspirin
Cyclooxygenase Inhibitors
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014