Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer

Phase 2

Completed

• Conditions: Rectal Neoplasm Carcinoma in Situ Adenocarcinoma
• Interventions: Drug: Metformin

• Registration Number: NCT03053544
• Lead Sponsor: Sunnybrook Health Sciences Centre

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-12-08
• Study First Submitted: 2016-12-20
• Study First Submitted QC: 2017-02-10
• Study First Posted: 2017-02-15
• Primary Completion: 2019-06-26
• Study Completion: 2019-06-26
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-25
• Last Update Posted: 2019-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	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.

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response (pCR) rate	1 year	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

Name	Time	Method
Tumor Proliferation Reduction	1 year	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	1 year	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.

Trial Locations

Locations (1)

Odette Cancer Centre, Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada