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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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.


Detailed Summary:
Sponsor: University Health Network, Toronto

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

Original Primary Outcome: Change in fractional hypoxic volume from first and second FAZA-PET scan. [ Time Frame: 7 days ]

Current Secondary Outcome:

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


Original Secondary Outcome:

  • Duration of time from randomization to the time of relapse or death [ Time Frame: 2 years ]
  • Number and types of acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation [ Time Frame: 90 days from the date of randomization ]
  • The average difference between the endogenous hypoxia marker levels from the first and second tumor biopsies [ Time Frame: Approximately 1 week apart ]
  • The average difference between the Ki-67 index from the first and second tumor biopsies [ Time Frame: Approximately 1 week apart ]


Information By: University Health Network, Toronto

Dates:
Date Received: March 16, 2015
Date Started: May 2015
Date Completion: May 2018
Last Updated: June 21, 2016
Last Verified: June 2016