Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer

NCT03053544 | Completed Phase 2 DMC

• 1 other identifier: 472-2015
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Rectal Neoplasm Carcinoma in Situ Adenocarcinoma

Keywords

rectal cancer; adenocarcinoma of the rectum; node positive rectal tumors; metformin; neoadjuvant chemoradiation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Tumor Proliferation Reduction

  1 year

• Tumor Hypoxia

  1 year

Study Arms (1)

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.

Drug: Metformin

Interventions

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.

Metformin

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Sunnybrook Research Institute: collaborator
• University of Toronto: collaborator

Study Sites (1)

Odette Cancer Centre, Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Shun Wong, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Marianne Koritzinsky, MD

  Princess Margaret Hospital, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: February 15, 2017
• Study Start: December 8, 2016
• Primary Completion: June 26, 2019
• Study Completion: June 26, 2019
• Last Updated: September 27, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)