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

This study is currently recruiting participants.
Verified June 2016 by University Health Network, Toronto
Sponsor:
ClinicalTrials.gov Identifier:
NCT02394652
First Posted: March 20, 2015
Last Update Posted: June 22, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
University Health Network, Toronto
  Purpose

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.


Condition Intervention Phase
Uterine Cervical Neoplasms Squamous Cell Carcinoma Adenocarcinoma Carcinoma, Adenosquamous Drug: Metformin Drug: Cisplatin Drug: FAZA Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • • 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 Measures:
  • 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 ]

Estimated Enrollment: 48
Study Start Date: May 2015
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

Drug: Metformin Drug: Cisplatin Drug: FAZA
Other Name: 18F-Fluoroazomycin arabinoside
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).

Drug: Cisplatin Drug: FAZA
Other Name: 18F-Fluoroazomycin arabinoside

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02394652


Contacts
Contact: Kathy Han, M.D., M.Sc. 416-946-2919

Locations
Canada, Alberta
Tom Baker Cancer Centre Not yet recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Corinne Doll, M.D.    403-521-3685      
Cross Cancer Institute Not yet recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Ericka Wiebe, M.D.    480-432-8755      
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Kathy Han, M.D., M.Sc.    416-946-2919      
Canada, Quebec
Hôpital Maisonneuve-Rosemont Not yet recruiting
Montréal, Quebec, Canada, H1T 2M4
Contact: Eve-Lyne Marchand, M.D., Ph.D.    514-252-3425      
Centre Hospitalier De L'Université de Montréal Not yet recruiting
Montréal, Quebec, Canada, H2L 4M1
Contact: Maroie Barkati, M.D.    514-890-8000 ext 28820      
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Kathy Han, M.D. Princess Margaret Cancer Centre
  More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02394652     History of Changes
Other Study ID Numbers: CXMET1
First Submitted: March 16, 2015
First Posted: March 20, 2015
Last Update Posted: June 22, 2016
Last Verified: June 2016

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Uterine Cervical Neoplasms
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Cisplatin
Metformin
Antineoplastic Agents
Hypoglycemic Agents
Physiological Effects of Drugs