The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial
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| ClinicalTrials.gov Identifier: NCT02394652 |
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Recruitment Status :
Recruiting
First Posted : March 20, 2015
Last Update Posted : January 18, 2020
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Uterine Cervical Neoplasms Squamous Cell Carcinoma Adenocarcinoma Carcinoma, Adenosquamous | Drug: Metformin Drug: Cisplatin Drug: FAZA | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 48 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | The Potential for Metformin to Improve Tumor Oxygenation in Locally Advanced Cervix Cancer: A Phase II Randomized Trial |
| Estimated Study Start Date : | May 2022 |
| Estimated Primary Completion Date : | December 2022 |
| Estimated Study Completion Date : | December 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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) |
Drug: Metformin
Metformin is an antidiabetic agent given orally. Drug: Cisplatin Cisplatin is an antineoplastic agent given intravenously. Drug: FAZA FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.
Other Name: 18F-Fluoroazomycin arabinoside |
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Active Comparator: 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). |
Drug: Cisplatin
Cisplatin is an antineoplastic agent given intravenously. Drug: FAZA FAZA is an investigational imaging agent for positron emission tomography scans indicated for hypoxia.
Other Name: 18F-Fluoroazomycin arabinoside |
- • Change in fractional hypoxic volume of the tumor on FAZA-PET scan before and after 1 week of metformin. [ Time Frame: About 7 days ]
- Disease-free survival [ Time Frame: 2 years ]
- Acute and late gastrointestinal and genitourinary toxicities following metformin and chemoradiation. [ Time Frame: 2 years ]
- Effect of metformin on endogenous hypoxia and other markers. [ Time Frame: About 7 days ]
- Biomarkers of response to metformin. [ Time Frame: 2 years ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02394652
| Contact: Kathy Han, M.D., M.Sc. | 416-946-2919 | kathy.han@uhn.ca |
| Canada, Alberta | |
| Tom Baker Cancer Centre | Not yet recruiting |
| Calgary, Alberta, Canada, T2N 4N2 | |
| Contact: Corinne Doll, M.D. 403-521-3685 | |
| Cross Cancer Institute | Not yet recruiting |
| Edmonton, Alberta, Canada, T6G 1Z2 | |
| Contact: Ericka Wiebe, M.D. 480-432-8755 | |
| Canada, Ontario | |
| Princess Margaret Cancer Centre | Recruiting |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Contact: Kathy Han, M.D., M.Sc. 416-946-2919 | |
| Canada, Quebec | |
| Hôpital Maisonneuve-Rosemont | Not yet recruiting |
| Montréal, Quebec, Canada, H1T 2M4 | |
| Contact: Eve-Lyne Marchand, M.D., Ph.D. 514-252-3425 | |
| Centre Hospitalier De L'Université de Montréal | Not yet recruiting |
| Montréal, Quebec, Canada, H2L 4M1 | |
| Contact: Maroie Barkati, M.D. 514-890-8000 ext 28820 | |
| Principal Investigator: | Kathy Han, M.D. | Princess Margaret Cancer Centre |
| Responsible Party: | University Health Network, Toronto |
| ClinicalTrials.gov Identifier: | NCT02394652 |
| Other Study ID Numbers: |
CXMET1 |
| First Posted: | March 20, 2015 Key Record Dates |
| Last Update Posted: | January 18, 2020 |
| Last Verified: | January 2020 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Carcinoma Uterine Cervical Neoplasms Carcinoma, Adenosquamous Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site |
Uterine Cervical Diseases Uterine Diseases Neoplasms, Complex and Mixed Metformin Fluoroazomycin arabinoside Hypoglycemic Agents Physiological Effects of Drugs Radiopharmaceuticals Molecular Mechanisms of Pharmacological Action |