Clinical trial NCT05536037: Metformin for the Prevention of Oral Cancer in Patients With Oral Premalignant Lesions
Official title: Metformin Chemoprevention of Oral Premalignant Lesions
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Erythroplakia
Leukoplakia
Oral Cavity Carcinoma
Proliferative Verrucous Leukoplakia
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2022-09-10
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This phase I trial tests whether metformin works in reducing the annual transformation (development of invasive cancer) of oral precancerous lesions into cancerous lesions. Metformin is a drug approved for the treatment of diabetes, but studies have shown that it may have some anticancer properties. Giving metformin may help prevent or slow the development of oral cancer from precancerous lesions.

Detailed description: PRIMARY OBJECTIVE:

I. To evaluate the transformation-free-survival in lesion types erythroplakia (EP) and verrucous hyperplasia (VH). 'Transformation' is defined as the development of invasive cancer.

SECONDARY OBJECTIVE:

I. To evaluate the current spontaneous regression rates, i.e., percentages of patients having lesion disappear within 1-year post treatment, in all four lesion types and compare them with historical documented regression rate in literature.

EXPLORATORY OBJECTIVE:

I. To evaluate the transformation-free-survival in lesion types homogenous leukoplakia (HL) and non-homogenous leukoplakia (NHL).

OUTLINE:

Patients receive metformin orally (PO) once daily (QD) on days 1-3 and then PO twice daily (BID) for up to 12 months in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 24 months.

Eligibility criteria: Inclusion Criteria:

* Age 18-85
* Clinical appearance of lesion

  * Homogenous leukoplakia
  * Non- homogenous leukoplakia
  * Erythroplakia
  * Proliferative verrucous leukoplakia
* Histologic appearance

  * No dysplasia
  * Mild dysplasia
  * Moderate dysplasia
  * Severe dysplasia
* Diabetics: if on metformin, will get them to 2000 mg per day, if not, will add metformin in consultation with endocrinologist
* All subjects must be able to comprehend and sign a written informed consent document
* Willing and able to be available for the duration of the study
* In general good health with no contraindication to biopsy or metformin therapy
* Laboratory results

Exclusion Criteria:

* Carcinoma in-situ, verrucous carcinoma, invasive squamous cell carcinoma (SCCa)
* Exclude systemic causes of the lesion: pemphigus, pemphigoid, systemic lupus erythematosus (SLE), lichenoid drug reaction, human immunodeficiency virus (HIV), syphilis
* Exclude local inciting factors: rule out (r/o) but allowing 2 weeks to pass and see if there is resolution, if not and doesn't resolve with local measures, medical treatment, enroll

  * Frictional: sharp tooth
  * Trauma
* Immunosuppression by natural illness or medically induced
* Hypersensitivity or allergic reaction to metformin or some other contraindication

Primary outcomes:
measure: Transformation-free-survival, in lesion types erythroplakia and verrucous hyperplasia
timeFrame: Up to 3 years
Secondary outcomes:
measure: Change in lesion status
timeFrame: Baseline to 1 year after treatment
Other outcomes:
measure: Transformation-free-survival, in lesion types homogenous leukoplakia and non-homogenous leukoplakia
timeFrame: Up to 3 years
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
References: