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

NCT02394652 | Completed Phase 2 DMC

• 1 other identifier: CXMET1
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• • Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin.

  About 7 days

Secondary Outcomes (4)

• 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

Study Arms (2)

Experimental: Metformin with Standard Chemoradiation

EXPERIMENTAL

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

Standard Chemoradiation

ACTIVE COMPARATOR

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

Interventions

Metformin DRUG

Metformin is an antidiabetic agent given orally.

Experimental: Metformin with Standard Chemoradiation

Cisplatin DRUG

Cisplatin is an antineoplastic agent given intravenously.

Experimental: Metformin with Standard Chemoradiation; Standard Chemoradiation

FAZA DRUG

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

Also known as: 18F-Fluoroazomycin arabinoside

Experimental: Metformin with Standard Chemoradiation; Standard Chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (5)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Centre Hospitalier De L'Université de Montréal

Montreal, Quebec, H2L 4M1, Canada

Location

MeSH Terms

Conditions

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

Interventions

Metformin; Cisplatin; fluoroazomycin arabinoside

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Kathy Han, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2015
• First Posted: March 20, 2015
• Study Start: May 21, 2015
• Primary Completion: January 12, 2021
• Study Completion: January 12, 2021
• Last Updated: April 21, 2021

Record last verified: 2021-04

Locations

CA (5)