Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer

Sunnybrook Health Sciences Centre

Status and phase: Completed; Phase 2

Conditions: Rectal Neoplasm Carcinoma in Situ Adenocarcinoma

Treatments: Drug: Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT03053544

472-2015

Details and patient eligibility

About

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

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

15 participants in 1 patient group

Metformin

Experimental group

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.

Treatment:

Drug: Metformin