Clinical trial NCT02325401: Dose-finding Study of Metformin With Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma
Official title: A Phase I Dose-finding Study of Metformin in Combination With Concurrent Cisplatin and Radiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Cancer
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2014-12-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* Locally advanced squamous cell cancer of the head and neck, stage III or IV disease (T1-2, N2a-3 or T3-4).
* Measurable disease
* No prior chemotherapy or radiation for head and neck squamous cell cancer
* Life expectancy of greater than 3 months.
* Adequate labs

Exclusion Criteria:

* Known metastatic disease.
* Nasopharyngeal carcinoma
* History of allergic reactions attributed to metformin or other agents used in study.
* Known diagnosis of diabetes requiring insulin for control.
* Administration of metformin within last 4 weeks.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Metformin in Combination With Concurrent Cisplatin and Radiation
timeFrame: 24 months
Secondary outcomes:
measure: Number of Participants Experiencing No-Reoccurrence at 36 Months
timeFrame: 36 months
measure: Number of Participants With Adverse Events
timeFrame: 36 months
measure: Progression Free Survival
timeFrame: 24 months
measure: Overall Survival
timeFrame: 24 months
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Trisha Wise-Draper, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Crist M, Yaniv B, Palackdharry S, Lehn MA, Medvedovic M, Stone T, Gulati S, Karivedu V, Borchers M, Fuhrman B, Crago A, Curry J, Martinez-Outschoorn U, Takiar V, Wise-Draper TM. Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition. J Immunother Cancer. 2022 Nov;10(11):e005632. doi: 10.1136/jitc-2022-005632.