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Did not obtain Health Canda approval for drug use in reasonable time and moved onward to new trial
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4-6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67 | Additional biomarker tested:
| 4-6 weeks |
| Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jewish General Hospital | Montreal | Quebec | H3T1E2 | Canada |
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| ID | Term |
|---|---|
| D016889 | Endometrial Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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Assess the effect of metformin on pre-treatment and post-treatment biomarkers in serum to determine the HOMA index
|
| 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:
| 4-6 weeks |
| Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK | Additional biomarker tested:
| 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:
| 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:
| 4-6 weeks |
| Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt | Additional biomarker tested:
| 4-6 weeks |
| Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR | Additional biomarker tested:
| 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:
| 4-6 weeks |
| D009369 |
| Neoplasms |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |