Neoplasms

Mouth and Tooth Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Mouth Neoplasms

Leukoplakia

Leukoplakia, Oral

Erythroplasia

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Precancerous Conditions

Pathological Conditions, Anatomical

Oral Cancer

Erythroplakia

Lip and Oral Cavity Cancer

Oral Leukoplakia

Hypoglycemic Agents

All Drugs and Chemicals

Metformin

Patients receive extended release metformin hydrochloride PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients will also undergo biopsies and blood collections on study.

Patients receive a placebo PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients will also undergo biopsies and blood collections on study.

Biopsy

Biospecimen Collection

Extended Release Metformin Hydrochloride

Placebo Administration

Shethal Bearelly

Scott M. Lippman

Christine H. Chung

Jennifer Gross

Cherie-Ann O. Nathan

Justine Moe

Frank G. Ondrey

Alexander R. Kerr

Miriam Rosin

Leigha Rock

Scott M Lippman

This phase IIb trial tests whether metformin works in preventing oral cancer in patients with oral leukoplakia (white patches) or erythroplakia (red patches). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in the blood. It decreases the amount of glucose patients absorb from food and the amount of glucose made by the liver. Metformin also increases the body's response to insulin, a natural substance that controls the amount of glucose in the blood. This trial may help researchers determine if metformin can stop changes in the mouth that are related to pre-cancer growths in the mouth.

PRIMARY OBJECTIVE:

I. To determine the histological response to metformin hydrochloride (metformin) intervention in the target lesion.

SECONDARY OBJECTIVES:

I. Clinical response to metformin intervention in the target lesion. II. Effect of metformin on cell proliferation (Ki67) and its molecular targets (pS6 and nuclear YAP) in the target lesion.

III. Metformin effect on serum metabolic markers (C-peptide, glucose and HbA1c).

IV. Trough plasma metformin concentrations.

EXPLORATORY OBJECTIVES:

I. Expression of dysregulated molecular mechanisms in the target lesion, including, in order of priority, p53, PTEN, p16, EGFR, and pEGFR.

II. Immune cell infiltration and markers of inflammation in the target lesion. III. Analysis of genomic alterations in the target lesion and blood deoxyribonucleic acid (DNA).

IV. Microbiome in oral rinses.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive extended release metformin hydrochloride orally (PO) once daily (QD) for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and biopsy at baseline and week 24.

ARM II: Patients receive a placebo PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and biopsy at baseline and week 24.

After completion of study treatment, patients are followed for up to 3 weeks.

Metformin for the Prevention of Oral Cancer in Patients With Oral Leukoplakia or Erythroplakia

M4OC-Prevent 2.0: Phase IIb Trial of Metformin for Oral Cancer Prevention

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Histologic response will be evaluated by the following criteria: complete response (CR): Complete reversal of dysplasia or hyperplasia to normal epithelium in the target lesion. Partial response (PR): Improvement of the degree of dysplasia or hyperplasia in the target lesion. No change (NC): No change in the degree of dysplasia or hyperplasia in the target lesion, anything that is not CR, PR or PD. Progressive disease (PD): Increase in the severity of grade of histology in the target lesion.

Clinical response will be evaluated by the following criteria: CR: disappearance of all evidence of lesion(s). PR: greater than or equal to 50% reduction in the sum of the products of diameters of lesion(s) measurable at baseline. Non-measurable lesion(s) may not increase greater than or equal to 25% in size and no new lesion may appear. NC: no change in the size of the lesion(s) identified at baseline and no new lesions appearing, i.e., anything that is not CR, PR, or PD. PD: any increase greater than or equal to 25% in the product of the diameters of any lesion(s) measurable at baseline or in the estimated size of lesion(s) nonmeasurable at baseline or the appearance of an unequivocal new lesion.

Effect of metformin on cell proliferation (Ki67) and its molecular targets (pS6 and nuclear YAP) in the target lesion. The change (pre to post) will be compared between arms.

Metformin effect on serum metabolic markers (C-peptide, glucose and HbA1c). The change (pre to post) in serum metabolic markers will be compared between arms.

The plasma metformin concentrations will be determined in the pre- and post-intervention samples.

National Cancer Institute (NCI)

University of Arizona

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Ductal

Carcinoma in Situ

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Adenocarcinoma

Breast Carcinoma In Situ

Patients fast for \>= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release PO QD until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).

Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).

Undergo collection of blood and tissue samples

Monitoring

Nutritional Assessment

Short-Term Fasting

Parijatham Thomas, MD

Andrea De Censi

Bernardo Bonanni

This phase IIb trial studies the combined effect of prolonged nightly fasting and metformin hydrochloride extended release in decreasing breast tumor cell proliferation and other biomarkers of breast cancer. Preventing invasive breast cancer or DCIS. Metformin is widely used to treat type II diabetes and is associated with a decreased risk of cancer and death in diabetic individuals. Intermittent fasting may protect cancer patients from the toxic effects of chemotherapy agents without causing chronic weight loss. The combination of intermittent fasting and metformin may reduce breast cancer growth and may be used in women at risk for breast cancer or other cancers associated with being overweight.

PRIMARY OBJECTIVES:

I. To assess the safety of the experimental intervention based on the frequency of occurrence of a dose limiting toxicity (DLT) in the first 14 participants assigned to the experimental treatment arm.

II. Evaluate the difference in post-treatment Ki67 labeling index (LI) in cancer adjacent ductal carcinoma in situ (DCIS) (in the presence of invasive breast cancer \[IBC\]), if present, or intraepithelial neoplasia (IEN) (defined as atypical ductal hyperplasia \[ADH\] or atypical lobular hyperplasia \[ALH\] or lobular carcinoma in situ \[LCIS\]) between the active treatment and the control group.

SECONDARY OBJECTIVES:

I. To explore the effect of intervention on the change of expression of PP2A-GSK3beta-MCL-1 axis in pre-post treatment cancer tissue levels.

II. To measure the change in circulating biomarkers: Homeostatic model assessment (HOMA) index, highly sensitive C-reactive protein (CRP) (hsCRP), C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, adipokines (leptin and adiponectin).

III. To correlate a customized next generation sequencing (NGS) mutational profile panel focused on estrogen receptor (ER) positive (+ve) with the response of Ki67.

IV. To measure the difference of cell death by immunohistochemistry (IHC) for M30 in post- treatment cancer samples between arms.

V. To measure the difference of phosphorylated (p)S6 by IHC in post- treatment cancer samples between arms.

VI. To assess safety and toxicities according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0.

VII. To correlate physiological distress, eating habits, tobacco and alcohol consumption with the response of Ki67 between arms.

VIII. To compare the area under the curve (AUC) of glucose levels between arms and within the experimental arm according to different doses of metformin hydrochloride extended release (0 mg, 750 mg and 1500 mg).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients fast for \>= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release orally (PO) once daily (QD) until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).

ARM II: Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).

After completion of study intervention, patients are followed up at 30 days.

Metformin and Nightly Fasting in Women With Early Breast Cancer

Time Restricted Eating And Metformin (TEAM) in Invasive Breast Cancer (IBC) or Ductal Carcinoma in Situ (DCIS). A Randomized, Phase IIb, Window of Opportunity Presurgical Trial.

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Defined as a hypoglycemic event requiring permanent discontinuation of study treatment or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug.

Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as body mass index \[BMI\] and HER2 status).

Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as BMI and HER2 status).

Will include Homeostatic model assessment index, highly sensitive C-reactive protein, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, leptin and adiponectin. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. Analysis of covariance (ANCOVA) models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.

Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.

Will depend upon next generation sequencing mutational profile obtained in post-treatment surgical specimens. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.

Will be assessed between arms. Will be assessed using IHC.

Will be correlated with response biomarkers.

Evaluated according to the Common Terminology Criteria for Adverse Events version 5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Metformin for the Prevention of Oral Cancer in Patients With Oral Leukoplakia or Erythroplakia	NCT05237960	Erythroplakia Oral Leukoplaki...	Biopsy Biospecimen Col... Extended Releas... Placebo Adminis...	21 Years -	University of Arizona
Metformin and Nightly Fasting in Women With Early Breast Cancer	NCT05023967	Anatomic Stage ... Anatomic Stage ... Breast Ductal C... Invasive Breast...	Biospecimen Col... Extended Releas... Monitoring Nutritional Ass... Short-Term Fast...	18 Years -	M.D. Anderson Cancer Center
Metformin and Nightly Fasting in Women With Early Breast Cancer	NCT05023967	Anatomic Stage ... Anatomic Stage ... Breast Ductal C... Invasive Breast...	Biospecimen Col... Extended Releas... Monitoring Nutritional Ass... Short-Term Fast...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for extended release metformin hydrochloride