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Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer

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ClinicalTrials.gov Identifier: NCT03053544
Recruitment Status : Completed
First Posted : February 15, 2017
Last Update Posted : September 27, 2019
Sponsor:
Collaborators:
Sunnybrook Research Institute
University of Toronto
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

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

Condition or disease Intervention/treatment Phase
Rectal Neoplasm Carcinoma in Situ Adenocarcinoma Drug: Metformin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer: An Internal Pilot Study
Study Start Date : December 8, 2016
Actual Primary Completion Date : June 26, 2019
Actual Study Completion Date : June 26, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
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.




Primary Outcome Measures :
  1. Pathological Complete Response (pCR) rate [ Time Frame: 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 :
  1. Tumor Proliferation Reduction [ Time Frame: 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.

  2. Tumor Hypoxia [ Time Frame: 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.



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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03053544


Locations
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Canada, Ontario
Odette Cancer Centre, Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Sunnybrook Research Institute
University of Toronto
Investigators
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Principal Investigator: Shun Wong, MD Sunnybrook Health Sciences Centre
Principal Investigator: Marianne Koritzinsky, MD Princess Margaret Hospital, Canada

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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT03053544     History of Changes
Other Study ID Numbers: 472-2015
First Posted: February 15, 2017    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Results from this internal pilot will be disseminated to participants and stakeholders by means of publication and presentation where appropriate.
Keywords provided by Sunnybrook Health Sciences Centre:
rectal cancer
adenocarcinoma of the rectum
node positive rectal tumors
metformin
neoadjuvant chemoradiation
Additional relevant MeSH terms:
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Adenocarcinoma
Rectal Neoplasms
Carcinoma in Situ
Adenocarcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs