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NCT Number: NCT02394652

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

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.

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Key information

Conditions

Uterine Cervical Neoplasms Adenocarcinoma Carcinoma Carcinoma, Adenosquamous Carcinoma, Squamous Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Complex and Mixed Neoplasms, Glandular and Epithelial Neoplasms, Squamous Cell Squamous Cell Carcinoma Urogenital Diseases Urogenital Neoplasms Uterine Cervical Diseases Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Tom Baker Cancer Centre, Calgary, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

metformin

Drug

Metformin is an antidiabetic agent given orally.

Cisplatin

Drug

Cisplatin is an antineoplastic agent given intravenously.

FAZA

Drug

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

Other names: 18F-Fluoroazomycin arabinoside

Primary outcomes

  1. • 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 outcomes

  1. Disease-free survival

    Time frame: 2 years

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

    Time frame: 2 years

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

    Time frame: About 7 days

  4. Biomarkers of response to metformin.

    Time frame: 2 years

Sponsors and collaborators

Lead sponsor

University Health Network, Toronto

Other

Registry information

Important dates

Study start
2015
Primary completion
2021
Study completion
2021
First posted
Mar 20, 2015
Registry last updated
Apr 21, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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