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

Squamous Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02394652
• Other study ID #: CXMET1
• Status: Completed
• Phase: Phase 2
• Start date: May 21, 2015
• Est. completion date: January 12, 2021

Study information

• Verified date: April 2021
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: January 12, 2021
• Est. primary completion date: January 12, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Adenosquamous
• Squamous Cell Carcinoma
• Uterine Cervical Neoplasms

Intervention

Drug:
• Metformin
Metformin is an antidiabetic agent given orally.
• Cisplatin
Cisplatin is an antineoplastic agent given intravenously.
• FAZA
FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Centre Hospitalier De L'Université de Montréal	Montréal	Quebec
Canada	Hôpital Maisonneuve-Rosemont	Montréal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	• Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin.		About 7 days
Secondary	Disease-free survival		2 years
Secondary	Acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation.		2 years
Secondary	Effect of metformin on endogenous hypoxia and other markers.		About 7 days
Secondary	Biomarkers of response to metformin.		2 years