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

NCT ID: NCT02394652

Last Updated: 2021-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-21
• Study Completion Date: 2021-01-12

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin is an antidiabetic agent given orally.

Cisplatin

Intervention Type: DRUG

Cisplatin is an antineoplastic agent given intravenously.

FAZA

Intervention Type: DRUG

FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.

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).

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

Cisplatin is an antineoplastic agent given intravenously.

FAZA

Intervention Type: DRUG

FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.

Interventions

Metformin

Metformin is an antidiabetic agent given orally.

Intervention Type: DRUG

Cisplatin

Cisplatin is an antineoplastic agent given intravenously.

Intervention Type: DRUG

FAZA

FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.

Intervention Type: DRUG

Other Intervention Names

18F-Fluoroazomycin arabinoside

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kathy Han, M.D.

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Centre Hospitalier De L'Université de Montréal

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

CXMET1

Identifier Type: -

Identifier Source: org_study_id