Back to resultsMetformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer
Primary Purpose
Rectal Neoplasm Carcinoma in Situ Adenocarcinoma
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Neoplasm Carcinoma in Situ Adenocarcinoma focused on measuring rectal cancer, adenocarcinoma of the rectum, node positive rectal tumors, metformin, neoadjuvant chemoradiation
Eligibility Criteria
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:
- Diagnosis of diabetes
- Current use of metformin
- Prior pelvic radiation
- Life expectancy < 6 months.
- Active infection
- Creatinine > 1.5X ULN, within 1 month prior to baseline
- AST, ALT > 2.5X ULN, within 1 month prior to baseline
- Bilirubin > 1.5 ULN, within 1 month prior to baseline
- Pregnant or breastfeeding women
Sites / Locations
- Odette Cancer Centre, Sunnybrook Health Sciences Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Metformin
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Tumor Hypoxia
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.
Full Information
NCT ID
NCT03053544
First Posted
December 20, 2016
Last Updated
September 25, 2019
Sponsor
Sunnybrook Health Sciences Centre
Collaborators
Sunnybrook Research Institute, University of Toronto
1. Study Identification
Unique Protocol Identification Number
NCT03053544
Brief Title
Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer
Official Title
Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer: An Internal Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
December 8, 2016 (undefined)
Primary Completion Date
June 26, 2019 (Actual)
Study Completion Date
June 26, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunnybrook Health Sciences Centre
Collaborators
Sunnybrook Research Institute, University of Toronto
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is a phase II, single arm, controlled, open label internal pilot.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Neoplasm Carcinoma in Situ Adenocarcinoma
Keywords
rectal cancer, adenocarcinoma of the rectum, node positive rectal tumors, metformin, neoadjuvant chemoradiation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metformin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pathological Complete Response (pCR) rate
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Tumor Proliferation Reduction
Description
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.
Time Frame
1 year
Title
Tumor Hypoxia
Description
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.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Diagnosis of diabetes
Current use of metformin
Prior pelvic radiation
Life expectancy < 6 months.
Active infection
Creatinine > 1.5X ULN, within 1 month prior to baseline
AST, ALT > 2.5X ULN, within 1 month prior to baseline
Bilirubin > 1.5 ULN, within 1 month prior to baseline
Pregnant or breastfeeding women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shun Wong, MD
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marianne Koritzinsky, MD
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Principal Investigator
Facility Information:
Facility Name
Odette Cancer Centre, Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Results from this internal pilot will be disseminated to participants and stakeholders by means of publication and presentation where appropriate.
Learn more about this trial
Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer
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