UMIN-CTR Clinical Trial

Basic information
Public title	Exploratory study on the anti-proliferative effects of metformin on endometrial cancer
Acronym	Exploratory study on the anti-proliferative effects of metformin on endometrial cancer
Scientific Title	Exploratory study on the anti-proliferative effects of metformin on endometrial cancer
Scientific Title:Acronym	Exploratory study on the anti-proliferative effects of metformin on endometrial cancer
Region	Japan

Condition
Condition	Endometrial cancer
Classification by specialty	Obsterics and gynecology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	Anti-proliferative effect of metformin on endometrial cancer tissues have been observed in patients with endometrial cancer. However, it is unclear how metformin affects endometrial cancer in vivo. The aim of this study is to evaluate the effect of metformin on H19 non-cording RNA expression, DNA methylation, and the activity of aromatase in endometrial cancer tissue and to investigate the anti-proliferative effects of metformin in patients with endometrial cancer.
Basic objectives2	Bio-availability
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	To evaluate the effect of metformin on H19 expression in endometrial cancer tissue
Key secondary outcomes	1. To evaluate the effect of metformin on DNA methylation in endometrial cancer tissue 2. To evaluate the effect of metformin on the activity of aromatase, expression of let7, c-myc Hmga2, lmp in endometrial cancer tissue 3. To evaluate the effect of metformin on the expression of biomarkers in the endometrium. 1) Differences in Ki67 and Topoisomerase IIa expression using immunohistochemistry. 2) Expression of PhosphorERK, PhosphorAKT, phosphor AMPK, phosphor-rpS6, cyclin D1 using western blot analysis 4. Evaluation of toxicity

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Prevention
Type of intervention	Medicine
Interventions/Control_1	1)Patients will receive a daily dose of metformin (initial dose, 500 mg/day; increased weekly up to 2250 mg/day in the absence of any adverse effects). 2)Metformin will be administered in patients who fulfill the eligibility criteria. Metfomin will be administrated in patients until a day prior to the operation. 3)Endometrial biopsy samples will be obtained before metformin administration (as baseline) and during operation.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	60 years-old >=
Gender	Female
Key inclusion criteria	1. Histologically confirmed grade 1-2 endometrioid adenocarcinoma 2. BMI over 25 and positive for insulin resistance 3.Over 20 years and under 60 years of age 4.Eastern Cooperative Oncology Group Performance status 0 5.Patient who are ready to provide written informed consent
Key exclusion criteria	1. Prior medical history of chemical sensitivity to metformin 2. Serum creatinine over1.0 mg/dl 3. History of lactic acidosis 4. Patients undergoing dialysis 5. Shock, cardiac arrest, cardiac infarction, thrombosis of the lung, or severe cardiovascular and/or lung damage 6. Ingestion of excessive amounts of alcohol 7. Elevated levels of AST(GOT), ALT(GPT) (over2 times upper limit of normal) 8. History of thrombosis 9. Mental illness that may require the administration of antipsychotics 10. Diabetes mellitus that requires medication 11. HbA1c over 8.0 12. Concomitant malignancies 13. Determined to be ineligible by the physician in charge for any other reason
Target sample size	15

Research contact person
Name of lead principal investigator	1st name Akira Middle name Last name Mitsuhashi
Organization	Graduate School of Medicine, Chiba University
Division name	Reproductive Medicine
Zip code	260-8670
Address	1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
TEL	043-222-7171
Email	antira@faculty.chiba-u.jp

Public contact
Name of contact person	1st name Akira Middle name Last name Mitsuhashi
Organization	Graduate School of Medicine, Chiba University
Division name	Reproductive Medicine
Zip code	260-8670
Address	1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
TEL	043-222-7171
Homepage URL
Email	antira@faculty.chbia-u.jp

Sponsor
Institute	Ciba University
Institute
Department

Funding Source
Organization	the Japan Society for Promotion of Science.
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	the institutional Review Board at Chiba University Hospital
Address	1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
Tel	043-222-7171
Email	hanaoka.hideki@faculty.chiba-u.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	千葉大学医学部附属病院

Other administrative information
Date of disclosure of the study information	2016 Year 02 Month 04 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	15
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2016 Year 01 Month 13 Day
Date of IRB	2016 Year 01 Month 12 Day
Anticipated trial start date	2016 Year 02 Month 04 Day
Last follow-up date	2019 Year 08 Month 01 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2016 Year 02 Month 03 Day
Last modified on	2020 Year 02 Month 06 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000024069