Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer

Rectal Neoplasm Carcinoma in Situ Adenocarcinoma Clinical Trial

Official title:

Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer: An Internal Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03053544
• Other study ID #: 472-2015
• Status: Completed
• Phase: Phase 2
• Start date: December 8, 2016
• Est. completion date: June 26, 2019

Study information

• Verified date: September 2019
• Source: Sunnybrook Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a phase II, single arm, controlled, open label internal pilot.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: June 26, 2019
• Est. primary completion date: June 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. Plan for care inclusive of:

i. standard of care neoadjuvant chemoradiation ii. planned total mesorectal excision (TME)

2. Histologically confirmed adenocarcinoma of the rectum

3. 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

4. ECOG performance status of 0 or 1

5. Provide written informed consent

6. 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:

1. Diagnosis of diabetes

2. Current use of metformin

3. Prior pelvic radiation

4. Life expectancy < 6 months.

5. Active infection

6. Creatinine > 1.5X ULN, within 1 month prior to baseline

7. AST, ALT > 2.5X ULN, within 1 month prior to baseline

8. Bilirubin > 1.5 ULN, within 1 month prior to baseline

9. Pregnant or breastfeeding women

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma in Situ
• Carcinoma in Situ
• Rectal Neoplasm Carcinoma in Situ Adenocarcinoma
• Rectal Neoplasms

Intervention

Drug:
• Metformin
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.

Locations

Country	Name	City	State
Canada	Odette Cancer Centre, Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Sunnybrook Research Institute, University of Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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
Secondary	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.	1 year