The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial

April 19, 2021 updated by: University Health Network, Toronto

Cervical cancer remains an important health problem worldwide. Poor tumor oxygenation (hypoxia) is associated with inferior survival in cervical cancer and resistance to radiation treatment. Hypoxia-modifying therapies improve survival, but existing therapies are impractical and/or toxic. Metformin, a non-toxic drug for diabetes, has been shown to decrease tumor hypoxia in animal studies and its use is associated with better survival in diabetic cancer patients. It is hypothesized that metformin may decrease cervical tumor hypoxia and thereby improve tumor response to radiation and survival in patients with locally advanced cervix cancer.

This is a randomized, multicenter phase II study of standard chemoradiation in combination with metformin versus standard chemoradiation alone in women with locally advanced cervix cancer. Women randomized to the metformin group will take metformin starting 1 week prior to standard chemoradiation and throughout the duration of external radiation treatment. Tumor hypoxia will be measured by a special X-ray test called positron emission test (PET) performed with a hypoxia dye called FAZA. The main purpose of this study is to see if metformin decreases tumor hypoxia measured on FAZA-PET; information about response and side effects will also be collected.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
    • Quebec
      • Montréal, Quebec, Canada, H1T 2M4
        • Hopital Maisonneuve-Rosemont
      • Montréal, Quebec, Canada, H2L 4M1
        • Centre Hospitalier de l'Universite de Montreal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologically confirmed squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervix, FIGO stage IB2-IVA
  • Planned for radical radiotherapy and concurrent cisplatin chemotherapy.
  • Able to receive weekly cisplatin.
  • No prior anticancer treatment for cervical cancer
  • ECOG 0 or 1
  • Life expectancy of greater than 3 months.
  • Normal organ and marrow function
  • Able to take oral medications.
  • Ability to understand and willing to sign the consent form
  • Willing to undergo biopsies of cervical tumor.

Exclusion Criteria:

  • Evidence of distant metastases
  • Receiving any other investigational agents concurrently or within 4 weeks.
  • Known diabetes mellitus.
  • Currently taking metformin, sulfonylureas, thiazolidinediones or insulin.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin or cisplatin.
  • Any condition associated with increased risk of metformin-associated lactic acidosis
  • Uncontrolled inter-current illness
  • Pregnant women
  • History of another invasive malignancy, except for non-melanoma skin cancer or tumors curatively treated with no evidence of disease for >=5 years.
  • Known HIV-positive
  • History of bowel obstruction or malabsorption syndromes
  • History of active clinically significant bleeding
  • Contraindications to radiotherapy
  • Taking drug disulfiram (antabuse).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: Metformin with Standard Chemoradiation

Metformin: About 1 week prior to the start of chemoradiation, take 850 mg of metformin, orally, once a day for 3 days, followed by 850 mg twice a day and continued for the duration of external radiation.

Chemoradiation: Cisplatin will be given intravenously at 40 mg/m2 week for 5 doses, concomitantly with external beam radiation.

FAZA-PET scan at baseline and after about 1 week of metformin (just prior to the start of chemoradiation)
Drug: Metformin
Metformin is an antidiabetic agent given orally.
Drug: Cisplatin
Cisplatin is an antineoplastic agent given intravenously.
Drug: FAZA
FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.
Other Names:
  • 18F-Fluoroazomycin arabinoside
Active Comparator: Standard Chemoradiation

Chemoradiation: Cisplatin will be given intravenously at 40 mg/m2 week for 5 doses, concomitantly with external beam radiation.

FAZA-PET scan at baseline and about 1 week later (just prior to the start of chemoradiation).
Drug: Cisplatin
Cisplatin is an antineoplastic agent given intravenously.
Drug: FAZA
FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.
Other Names:
  • 18F-Fluoroazomycin arabinoside

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
• Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin.
Time Frame: About 7 days
About 7 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease-free survival
Time Frame: 2 years
2 years
Acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation.
Time Frame: 2 years
2 years
Effect of metformin on endogenous hypoxia and other markers.
Time Frame: About 7 days
About 7 days
Biomarkers of response to metformin.
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Kathy Han, M.D., Princess Margaret Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 21, 2015

Primary Completion (Actual)

January 12, 2021

Study Completion (Actual)

January 12, 2021

Study Registration Dates

First Submitted

March 16, 2015

First Submitted That Met QC Criteria

March 16, 2015

First Posted (Estimate)

March 20, 2015

Study Record Updates

Last Update Posted (Actual)

April 21, 2021

Last Update Submitted That Met QC Criteria

April 19, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CXMET1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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