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| Name | Class |
|---|---|
| Sunnybrook Research Institute | OTHER |
| University of Toronto | OTHER |
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This study is a phase II, single arm, controlled, open label internal pilot.
This internal pilot will be the first prospective study to assess the feasibility and efficacy of adding metformin in non-diabetic rectal patients who undergo standard of care neoadjuvant chemoradiation therapy (CRT). The translational aim of the study will inform on predictive factors (such as p53) and mechanism of action (hypoxia, proliferation). Metformin has been used for decades in patients with type 2 diabetes and has an extremely safe toxicity profile. With current interest in the use of metformin as a cancer therapeutic in non-diabetics, this study is expected to provide proof-of principle data for a larger study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin | Experimental | Participants will self-administer 500mg metformin twice daily by mouth: 1) beginning 1 to 2 weeks prior to standard of care CRT, 2) during standard of care CRT and 3) until 30 days after the end of standard of care CRT. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Participants will self-administer 500mg metformin twice daily by mouth: 1) beginning 1-2 weeks prior to standard of care CRT, 2) during standard of care CRT and 3) until 30 days after the end of standard of care CRT. |
| Measure | Description | Time Frame |
|---|---|---|
| Pathological Complete Response (pCR) rate | The primary outcome is to evaluate the use of metformin to improve pathological complete response (pCR) rates in non-diabetic participants undergoing standard of care neoadjuvant CRT for rectal cancer. The primary outcome will be measured by the pathological complete response rate after completion of the study treatment. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Proliferation Reduction | The secondary outcome is to determine if metformin reduces tumor proliferation in this study population. The secondary outcome will be determined by examining tumor cell proliferation from longitudinal biopsy specimens. | 1 year |
| Tumor Hypoxia |
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Inclusion Criteria:
Plan for care inclusive of:
i. standard of care neoadjuvant chemoradiation ii. planned total mesorectal excision (TME)
Histologically confirmed adenocarcinoma of the rectum
At least one of the following:
i. T3 or T4 lesions ii. T2 lesions ≤ 1 mm to the mesorectal fascia iii. Node positive rectal tumor
ECOG performance status of 0 or 1
Provide written informed consent
Female participants of childbearing potential agree to use adequate methods of contraception from the start of metformin administration until the start of CRT. Contraception will not be required to be continued during or after CRT as this treatment renders participants infertile. Clinically acceptable methods of birth control for this study include intrauterine devices (IUD), birth control pills, hormonal implants, injectable contraceptives, and using barrier methods such as condoms, vaginal diaphragm with spermicide, or sponge.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shun Wong, MD | Sunnybrook Health Sciences Centre | Principal Investigator |
| Marianne Koritzinsky, MD | Princess Margaret Hospital, Canada | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Odette Cancer Centre, Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
Results from this internal pilot will be disseminated to participants and stakeholders by means of publication and presentation where appropriate.
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| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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The secondary outcome is to determine if metformin reduces tumor hypoxia in this study population. The secondary outcome will be determined by examining tumor cell hypoxia from longitudinal biopsy specimens. |
| 1 year |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |