Dose-finding Study of Metformin With Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT02325401 | Completed Phase 1 Results DMC

• 1 other identifier: UCCI-HN-14-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (4)

• Number of Participants Experiencing No-Reoccurrence at 36 Months

  36 months

• Number of Participants With Adverse Events

  36 months

• Progression Free Survival

  24 months

• Overall Survival

  24 months

Study Arms (1)

Metformin with Chemoradiation

EXPERIMENTAL

Metformin administered orally daily to start one week prior to Cisplatin and Radiation Therapy. Metformin dose is escalating.

Drug: Metformin; Drug: Cisplatin; Radiation: Radiation Therapy

Interventions

Metformin DRUG

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.

Also known as: Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet

Metformin with Chemoradiation

Cisplatin DRUG

Dosed at 100mg/m2 on days 1, 22, and 43

Also known as: Platinol, Platinol-AQ

Metformin with Chemoradiation

Radiation Therapy RADIATION

70 Gy in 2 Gy once daily fractions of 35 fractions

Metformin with Chemoradiation

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (1)

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

Location

Related Publications (1)

• 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.

  PMID: 36328378 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Metformin; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Trisha Wise-Draper M.D., Ph.D., Associate Professor of Medicine, Medical Director of the UC Cancer C
• Organization: University of Cincinnati

wiseth@ucmail.uc.edu

(513) 558-2826

Study Officials

• Trisha Wise-Draper, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 16, 2014
• First Posted: December 25, 2014
• Study Start: May 11, 2015
• Primary Completion: December 26, 2017
• Study Completion: February 21, 2020
• Last Updated: June 11, 2020
• Results First Posted: June 11, 2020

Record last verified: 2020-05

Locations

US (1)