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

Primary Purpose

Uterine Cervical Neoplasms, Squamous Cell Carcinoma, Adenocarcinoma

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Metformin
Cisplatin
FAZA
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uterine Cervical Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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).

Sites / Locations

  • Tom Baker Cancer Centre
  • Cross Cancer Institute
  • Princess Margaret Cancer Centre
  • Hôpital Maisonneuve-Rosemont
  • Centre Hospitalier De L'Université de Montréal

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental: Metformin with Standard Chemoradiation

Standard Chemoradiation

Arm Description

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)

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).

Outcomes

Primary Outcome Measures

• Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin.

Secondary Outcome Measures

Disease-free survival
Acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation.
Effect of metformin on endogenous hypoxia and other markers.
Biomarkers of response to metformin.

Full Information

First Posted
March 16, 2015
Last Updated
April 19, 2021
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT02394652
Brief Title
The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial
Official Title
The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
May 21, 2015 (Actual)
Primary Completion Date
January 12, 2021 (Actual)
Study Completion Date
January 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uterine Cervical Neoplasms, Squamous Cell Carcinoma, Adenocarcinoma, Carcinoma, Adenosquamous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental: Metformin with Standard Chemoradiation
Arm Type
Experimental
Arm Description
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)
Arm Title
Standard Chemoradiation
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Metformin is an antidiabetic agent given orally.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin is an antineoplastic agent given intravenously.
Intervention Type
Drug
Intervention Name(s)
FAZA
Other Intervention Name(s)
18F-Fluoroazomycin arabinoside
Intervention Description
FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.
Primary Outcome Measure Information:
Title
• Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin.
Time Frame
About 7 days
Secondary Outcome Measure Information:
Title
Disease-free survival
Time Frame
2 years
Title
Acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation.
Time Frame
2 years
Title
Effect of metformin on endogenous hypoxia and other markers.
Time Frame
About 7 days
Title
Biomarkers of response to metformin.
Time Frame
2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathy Han, M.D.
Organizational Affiliation
Princess Margaret Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Hôpital Maisonneuve-Rosemont
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Centre Hospitalier De L'Université de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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