Endometrial CancerPhase 2NCT02042495
Endometrial Cancer Biomarker Changes Following Exposure to Metformin
A Phase 2 study testing Metformin in people with Endometrial Cancer, run by Jewish General Hospital at 1 site in Canada.
Trial summary
The investigators will explore the chemopreventive role of metformin. The purpose of this study is to determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in… Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Endometrial Cancer
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2016to Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a confirmed diagnosis of endometrial cancer based on an endometrial sampling though biopsy or dilatation and curettage
- Must be able to undergo appropriate surgical staging for endometrial cancer
- Must consent to be in the study and must have signed and dated an IRB-approved consent form conforming to government and institutional guidelines
Who cannot join
- Patients with a contraindication to receiving metformin treatment
- Patients with cognitive impairment
- Renal or hepatic functioning > 125% upper limit of normal
- Currently on medications for metabolic diseases, such as diabetes mellitus
- History of lactic acidosis
- Treatment with medications that may increase metformin levels: cationic drugs, e.g., digoxin, amiloride, procainamide, trimethoprim, vancomycin, triamterene, and morphine
- History of chronic alcohol abuse
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Clinical Trial to Evaluate Endometrial Cancer Biomarker Changes Following Exposure to the Insulin Sensitizer Metformin
The investigators will explore the chemopreventive role of metformin. The purpose of this study is to determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in endometrial cancer tissue. This is a phase IIa study of metformin to be used to the pre-operative period of women diagnosed with endometrial cancer by comparing their endometrial biopsy specimens taken at their initial visit and after 4-6 weeks of treatment of metformin on the day of their surgical staging.
Read the detailed description
Aim 1 To determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in endometrial cancer tissue.
Aim II To compare specified biomarkers in each endometrial cancer patient before and after receiving metformin. Our goal is to compare the following biomarkers in each patient before and after metformin administration: Ki-67, TUNEL assay for apoptosis level, phosphor-AMPK, phosphor-IGF-1R, phosphor-IRS1, phospho-Akt, phospho-S6, phosphor-mTOR, pACC.
All patients diagnosed with endometrial cancer presenting to the Jewish General Hospital for surgical treatment will be invited to participate.
- Conditions
- Endometrial Cancer
- Being tested
- Metformin
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called glucophage
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin 500 mg PO TID from time of entry to study until scheduled surgical staging operation.
In cases of unresolving side effects, the metformin will be dose reduced to metformin 500 mg PO BID with evaluation after 1 week followed by withdrawal from the study if side effects persist. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in phosphorylated-S6
Paired-t test will be used to determine the effect of oral metformin on the phosphorylated-S6 in pre-treatment and post-treatment endometrial samples.
Measured: 4-6 weeks
Secondary outcomes (9)
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67
Additional biomarker tested:
- Ki-67
Measured: 4-6 weeks
Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index
Assess the effect of metformin on pre-treatment and post-treatment biomarkers in serum to determine the HOMA index
- fasting IGF-I
- fasting insulin
- fasting IGFBP-1
- fasting glucose levels
Measured: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay
Additional biomarker tested:
- TUNEL assay for apoptosis level
Measured: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK
Additional biomarker tested:
- phosphorylated-AMPK
Measured: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R
Additional biomarker tested:
- phosphorylated-IGF-1R
Measured: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated insulin-receptor substrate protein 1 (phosphor-IRS1)
Additional biomarker tested:
- phosphor-IRS1
Measured: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt
Additional biomarker tested:
- phospho-Akt
Measured: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR
Additional biomarker tested:
- phosphor-mTOR
Measured: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated acetyl-CoA carboxylase (pACC)
Additional biomarker tested:
- pACC
Measured: 4-6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2014 (estimated)
- Study startAug 2016
- Primary completionDec 2017 (estimated)
Why it stopped: Did not obtain Health Canda approval for drug use in reasonable time and moved onward to new trial
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jewish General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shannon Salvador, Jewish General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02042495
- Sponsor's protocol ID
- JGH-140111
- Status last verified
- Aug 2016
- First submitted
- 12 Jan 2014
- Last updated
- 30 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial to Evaluate Endometrial Cancer Biomarker Changes Following Exposure to the Insulin Sensitizer Metformin
- ClinicalTrials.gov ID
- NCT02042495
- Acronym / sponsor ID
- JGH-140111
- Conditions
- Endometrial Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Did not obtain Health Canda approval for drug use in reasonable time and moved onward to new trial
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jewish General HospitalUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- Dec 2017 (estimated)
- First posted
- 23 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will explore the chemopreventive role of metformin. The purpose of this study is to determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in endometrial cancer tissue. This is a phase IIa study of metformin to be used to the pre-operative period of women diagnosed with endometrial cancer by comparing their endometrial biopsy specimens taken at their initial visit and after 4-6 weeks of treatment of metformin on the day of their surgical staging.
Detailed description
Aim 1 To determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in endometrial cancer tissue.
Aim II To compare specified biomarkers in each endometrial cancer patient before and after receiving metformin. Our goal is to compare the following biomarkers in each patient before and after metformin administration: Ki-67, TUNEL assay for apoptosis level, phosphor-AMPK, phosphor-IGF-1R, phosphor-IRS1, phospho-Akt, phospho-S6, phosphor-mTOR, pACC.
All patients diagnosed with endometrial cancer presenting to the Jewish General Hospital for surgical treatment will be invited to participate.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminMetformin 500 mg PO TID from time of entry to study until scheduled surgical staging operation. In cases of unresolving side effects, the metformin will be dose reduced to metformin 500 mg PO BID with evaluation after 1 week followed by withdrawal from the study if side effects persist. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Have a confirmed diagnosis of endometrial cancer based on an endometrial sampling though biopsy or dilatation and curettage
- Must be able to undergo appropriate surgical staging for endometrial cancer
- Must consent to be in the study and must have signed and dated an IRB-approved consent form conforming to government and institutional guidelines
Key exclusion criteria (7 listed)
- Patients with a contraindication to receiving metformin treatment
- Patients with cognitive impairment
- Renal or hepatic functioning > 125% upper limit of normal
- Currently on medications for metabolic diseases, such as diabetes mellitus
- History of lactic acidosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: glucophage | Drug | Metformin |
Primary outcome
Change in phosphorylated-S6
Time frame: 4-6 weeks
Paired-t test will be used to determine the effect of oral metformin on the phosphorylated-S6 in pre-treatment and post-treatment endometrial samples.
9 secondary outcomes
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67
Time frame: 4-6 weeks
Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index
Time frame: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay
Time frame: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK
Time frame: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R
Time frame: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated insulin-receptor substrate protein 1 (phosphor-IRS1)
Time frame: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt
Time frame: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR
Time frame: 4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated acetyl-CoA carboxylase (pACC)
Time frame: 4-6 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Endometrial Cancer, run by Jewish General Hospital at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in phosphorylated-S6 (time frame: 4-6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2016.