Clinical trial NCT02394652: The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial
Official title: The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Uterine Cervical Neoplasms
Squamous Cell Carcinoma
Adenocarcinoma
Carcinoma, Adenosquamous
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2015-03-20
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: • Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin.
timeFrame: About 7 days
Secondary outcomes:
measure: Disease-free survival
timeFrame: 2 years
measure: Acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation.
timeFrame: 2 years
measure: Effect of metformin on endogenous hypoxia and other markers.
timeFrame: About 7 days
measure: Biomarkers of response to metformin.
timeFrame: 2 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier De L'Université de Montréal
state: Quebec
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Kathy Han, M.D.
role: PRINCIPAL_INVESTIGATOR
References: