PREMIUM (PRE-Surgical Metformin In Uterine Malignancies) study

ISRCTN	ISRCTN88589234
DOI	https://doi.org/10.1186/ISRCTN88589234
Clinical Trials Information System (CTIS)	2014-000991-25
Protocol serial number	17351
Sponsor	Central Manchester University Hospitals NHS Trust (CMFT)
Funder	National Institute for Health Research

Submission date: 04/03/2015
Registration date: 05/03/2015
Last edited: 18/07/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-metformin-before-surgery-for-womb-cancer

Contact information

Mr Richard Hutson
Public

Manchester Academic Health Science Centre
The Christie NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX
United Kingdom

Study information

Primary study design	Interventional
Study design	Randomised; Interventional; Design type: Treatment
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Presurgical metformin for women with endometrial cancer: a randomised placebo controlled trial
Study objectives	Randomised placebo-controlled trial looking to determine whether metformin inhibits cellular growth in endometrial cancer and severe atypical endometrial hyperplasia. It will also look at the biological effects of metformin in endometrial cancer and hyperplasia.
Ethics approval(s)	NRES Committee North west-Haydock, 23/09/2014, ref: 14/NW/1236
Health condition(s) or problem(s) studied	Topic: Cancer; Subtopic: Gynaecological Cancer; Disease: Uterus/Endometrium
Intervention	Metformin 850mg or placebo given once daily for 3 days and then twice a day until surgery
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Metformin
Primary outcome measure(s)	Tumour analysis - Ki-67; Timepoint(s): screening and pre operative
Key secondary outcome measure(s)	1. Physiological analyses - insulin resistance and obesity markers; Timepoint(s): Screening and pre operative 2. Tolerability of treatment; Timepoint(s): pre operative 3. Tumour analysis - Apoptotic markers; Timepoint(s): screening and pre operative 4. Tumour analysis - PI3K-Akt-mTOR signal transduction pathway molecules; Timepoint(s): screening and pre operative
Completion date	31/10/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	90
Key inclusion criteria	1. Biopsy-proven type 1 endometrial carcinoma or severe atypical endometrial hyperplasia 2. Scheduled surgical treatment by hysterectomy in 5-35 days’ time 3. Informed consent 4. Age 18 years or more
Key exclusion criteria	1. Current treatment with metformin 2. Diabetic on hypoglycaemic medication 3. Inability to consent due to lack of capacity or language barriers 4. Unable to comply with treatment protocol 5. Type 2 endometrial cancer 6. Severe renal impairment (Serum creatinine >130umol/L or eGFR < 45ml/min/1.732m2) 7. Severe hepatic impairment (abnormal LFTs to be discussed on case by case basis with hepatologist) 8. Current alcohol abuse 9. Sensitivity/hypersensitivity to biguanides 10. Current treatment with other mTOR inhibitors or chemotherapeutic agents
Date of first enrolment	06/02/2015
Date of final enrolment	02/03/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Central Manchester Foundation Trust (lead site)

Manchester
M13 9WL
United Kingdom

Wrightington, Wigan and Leigh NHS Foundation Trust

Wigan, Lancashire
WN1 2NN
United Kingdom

Christie Hospital NHS Foundation Trust

Manchester
M20 4BX
United Kingdom

Pennine Acute Hospitals NHS Trust

Manchester
M8 5RB
United Kingdom

Tameside General Hospital

Ashton-under-Lyne
OL6 9RW
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Lynne Webster (lynne.webster@cmft.nhs.uk).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	15/04/2019		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			18/07/2019	No	Yes

Editorial Notes

18/07/2019: Link to results added to results (plain English).
29/01/2019: Publication reference added.
04/04/2017: The recruitment end date was changed from 31/10/2017 to 02/03/2017.