Adenocarcinoma, Carcinoma, Adenosquamous, Squamous Cell Carcinoma, Uterine Cervical Neoplasms
Conditions
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.
Interventions
DRUGMetformin
Metformin is an antidiabetic agent given orally.
DRUGCisplatin
Cisplatin is an antineoplastic agent given intravenously.
DRUGFAZA
FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin. | About 7 days |
Secondary
| Measure | Time frame |
|---|---|
| Disease-free survival | 2 years |
| Acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation. | 2 years |
| Effect of metformin on endogenous hypoxia and other markers. | About 7 days |
| Biomarkers of response to metformin. | 2 years |
Countries
Canada
Outcome results
None listed