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Uterine Cervical NeoplasmsPhase 2NCT02394652

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

A Phase 2 study testing Metformin, Cisplatin and FAZA in people with Uterine Cervical Neoplasms and Squamous Cell Carcinoma, run by University Health Network, Toronto at 5 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Metformin, Cisplatin and FAZA
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
5 sitesCanada
Study dates
21 May 2015to 12 Jan 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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).

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Canada5 sites
  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Hôpital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • Centre Hospitalier De L'Université de Montréal

    Montreal, Quebec, H2L 4M1

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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.

Being tested
Metformin, Cisplatin, FAZA
Medical subject headings
Uterine Cervical Neoplasms, Carcinoma, Squamous Cell, Adenocarcinoma, Carcinoma, Adenosquamous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Metformin is an antidiabetic agent given orally.

  • CisplatinDrug

    Cisplatin is an antineoplastic agent given intravenously.

  • FAZADrug

    Also called 18F-Fluoroazomycin arabinoside

    FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.

Study groups in NCT02394652
Study groupRoleWhat they receive
Experimental: Metformin with Standard ChemoradiationExperimentalMetformin: 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)
Receives: Drug: Metformin; Drug: Cisplatin; Drug: FAZA
Standard ChemoradiationActive comparatorChemoradiation: 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).
Receives: Drug: Cisplatin; Drug: FAZA

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: About 7 days

Secondary outcomes (4)
  1. Disease-free survival

    Measured: 2 years

  2. Acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation.

    Measured: 2 years

  3. Effect of metformin on endogenous hypoxia and other markers.

    Measured: About 7 days

  4. Biomarkers of response to metformin.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2015 (estimated)
  2. Study start21 May 2015
  3. Primary completion12 Jan 2021
  4. Study completion12 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02394652
Sponsor's protocol ID
CXMET1
Status last verified
Apr 2021
First submitted
16 Mar 2015
Last updated
21 Apr 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin, Cisplatin and FAZA in people with Uterine Cervical Neoplasms and Squamous Cell Carcinoma, run by University Health Network, Toronto at 5 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

• Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin. (time frame: About 7 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2021.

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