The purpose of this research study is to test the safety of adding metformin to standard of care. The standard of care treatment will be cisplatin once every 3 weeks for 3 treatments and radiation for 7 weeks. Metformin is a medication that is currently used to treat diabetes. Increasing amounts of metformin will be given to groups of patients already receiving normal treatment for their cancer to see if metformin causes any good effects by killing your cancer or bad effects (side effects).
Patients were registered by contacting the University of Cincinnati Clinical Trials Office. Patients must be registered and consent obtained prior to initiation of any protocol therapy. Treatment was administered on an outpatient basis. Adverse events and potential risks for metformin and cisplatin and radiation were reported. Patients must have screening labs performed within 2 weeks of start of treatment including a complete blood count, liver function tests, metabolic renal panel including magnesium, vitamin B12 level, lactate, and C-peptide. Renal panel must be verified within 24 hours of cisplatin administration. They must fulfill inclusion criteria. The recommended starting dose of metformin in diabetic patients is 500mg orally twice a day which can be escalated by 500mg increments weekly as tolerated with the maximum recommended daily dose of 2550mg. Cisplatin was given either before or after the radiation therapy fraction that is given on the same day. If radiation is held for more than 2 days (for any reason), cisplatin may be held as well until radiation resumes. The prescribed radiotherapy dose was be 70 Gy in 2 Gy once-daily fraction size (total of 35 fractions).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Escalating doses of 2000mg, 2550 mg and 3000mg. Starting 1 week prior to the initiation of chemoradiation and ending the final day of chemo or radiation.
Dosed at 100mg/m2 on days 1, 22, and 43
70 Gy in 2 Gy once daily fractions of 35 fractions
University of Cincinnati Cancer Institute
Cincinnati, Ohio, United States
Maximum Tolerated Dose (MTD) of Metformin in Combination With Concurrent Cisplatin and Radiation
Cohorts of patients received escalating doses of metformin (2000 mg, 2550 mg, or 3000 mg divided into daily doses) with a 7-day to 14-day lead-in prior to CRT based on the modified toxicity probability interval design to allow for possible re-escalation after previous de-escalation and to maximize the ability to identify the maximum tolerated dose (MTD). Patients continued to receive metformin for the duration of CRT as tolerated.
Time frame: 24 months
Number of Participants Experiencing No-Reoccurrence at 36 Months
Patients were evaulated at 36 months to determine if there was recurrence of disease.
Time frame: 36 months
Number of Participants With Adverse Events
Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.Any participants with any adverse event at any grade was included. Adverse events were collected during the on study period of 21 weeks up to three months after the study for a total of 34 weeks.
Time frame: 36 months
Progression Free Survival
2-year progression free survival
Time frame: 24 months
Overall Survival
2 year overall survival
Time frame: 24 months
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