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

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ClinicalTrials.gov Identifier: NCT02394652
Recruitment Status : Recruiting
First Posted : March 20, 2015
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE March 16, 2015
First Posted Date  ICMJE March 20, 2015
Last Update Posted Date January 18, 2020
Estimated Study Start Date  ICMJE May 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 14, 2015)
• 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 Measures  ICMJE
 (submitted: March 16, 2015)
Change in fractional hypoxic volume from first and second FAZA-PET scan. [ Time Frame: 7 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2015)
  • 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 Measures  ICMJE
 (submitted: March 16, 2015)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial
Official Title  ICMJE 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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Uterine Cervical Neoplasms
  • Squamous Cell Carcinoma
  • Adenocarcinoma
  • Carcinoma, Adenosquamous
Intervention  ICMJE
  • 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 Name: 18F-Fluoroazomycin arabinoside
Study Arms  ICMJE
  • 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)

    Interventions:
    • Drug: Metformin
    • Drug: Cisplatin
    • Drug: FAZA
  • 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).

    Interventions:
    • Drug: Cisplatin
    • Drug: FAZA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 16, 2015)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kathy Han, M.D., M.Sc. 416-946-2919 kathy.han@uhn.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02394652
Other Study ID Numbers  ICMJE CXMET1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kathy Han, M.D. Princess Margaret Cancer Centre
PRS Account University Health Network, Toronto
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP