Clinical trial NCT03053544: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rectal Neoplasm Carcinoma in Situ Adenocarcinoma
Keywords: rectal cancer
adenocarcinoma of the rectum
node positive rectal tumors
metformin
neoadjuvant chemoradiation
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Sunnybrook Research Institute
name: University of Toronto
First posted: 2017-02-15
Enrollment: 15
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pathological Complete Response (pCR) rate
timeFrame: 1 year
Secondary outcomes:
measure: Tumor Proliferation Reduction
timeFrame: 1 year
measure: Tumor Hypoxia
timeFrame: 1 year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Odette Cancer Centre, Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Shun Wong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Hospital, Canada
name: Marianne Koritzinsky, MD
role: PRINCIPAL_INVESTIGATOR
References: