Head and Neck Cancer, Head and Neck Carcinoma, Oral Cancer, Oral Squamous Cell Carcinoma
Conditions
Keywords
Metronidazole, Chlorhexidine
Brief summary
The goal of this phase II single arm clinical study is to evaluate the effect of antibiotics (metronidazole) and oral chlorhexidine (CHX) in reducing the bacteria load within tumors of patients undergoing surgery for oral cancer.
Detailed description
The prognosis for patients with locally advanced, non-Human Papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) remains poor. The immunosuppressive tumor immune microenvironment in HNSCC presents a significant barrier to both conventional and immune-based therapies. Recent studies have indicated that dysbiotic oral microbiota, particularly in the context of periodontal disease, can contribute to chronic oral mucosal inflammation and the recruitment of suppressive immune cell infiltrates. Bacterial-induced chronic inflammation may play a crucial role in treatment resistance in HNSCC. Understanding the impact of microbial modulation on the tumor immune microenvironment in HNSCC could lead to the identification of novel therapeutic targets. In this single-arm phase II clinical trial, oral cancer patients will be treated with oral metronidazole and CHX rinses prior to surgery. Investigator will assess the ability for the treatment to reduce the absolute amount of intratumoral bacteria and evaluate changes in the intratumoral bacterial community and infiltrating immune cells.
Interventions
DRUGMetronidazole
Participants will receive metronidazole (500 mg t.i.d. x 10 days)
OTHERChlorhexidine
Mouth rinse chlorhexidine (10 ml t.i.d. x 10 days)
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed squamous cell carcinoma of the oral cavity * Must have planned surgery for curative intent * Participants ≥ 18 years of age * Participants must have the ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Known allergy to metronidazole and/or chlorhexidine * Severe liver or kidney disease as determined by history of laboratory tests * Participants actively drinking alcohol (unable to abstain for the 10 day antibiotic period) * Recurrent oral cancer after prior radiation or chemoradiation * Participants with unresectable oral cancer * Participants unable to tolerate oral rinse or unable to have metronidazole administered by mouth or by feeding tube * Participants currently or have taken other antibiotics within the prior 30 days * Participant is pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in absolute amount of intraumoral bacteria as quantified by 16S rRNA qPCR | Baseline, surgery (10 days post intervention) | The difference between pre-treatment and post-treatment tumor bacteria burden will be assessed. |
Secondary
| Measure | Time frame |
|---|---|
| Change in absolute amount of intraumoral bacteria in post treatment participants compared to control patients as quantified by 16S rRNA qPCR | Baseline, surgery (10 days post intervention) |
| Disease-free survival | Time from date of randomization to recurrence, second primary malignancy, or death, as determined by standard of care surveillance, up to three years. |
| Overall Survival | Time from date of randomization to recurrence, second primary malignancy, or death, as determined by standard of care surveillance, up to three years. |
Countries
United States
Contacts
CONTACTNatalie Silver, MD
PRINCIPAL_INVESTIGATORNatalie Silver, MD
Case Comprehensive Cancer Center, Cleveland Clinic Foundation
Outcome results
None listed