Phase I/II Study OF Metformin in Combination With Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma

Phase 1

Completed

Conditions: Head and Neck Squamous Cell Carcinoma

Interventions: Drug: Metformin

Registration Number: NCT02949700

Lead Sponsor: Baylor College of Medicine

Brief Summary: The purpose of this research is to see whether metformin can improve the response rate in patients undergoing chemotherapy and radiation for squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx. The purpose of this research is also to see the effects, good and bad, of metformin therapy for this disease. Researchers will also analyze tumor and blood samples from study patients to test and understand the characteristics of tumors which respond to metformin.

Detailed Description: Information from laboratory studies and retrospective studies of patients with this disease has shown that the addition of metformin (a commonly used medicine for treating diabetes) to chemotherapy and radiation can improve the rate at which the cancer responds to treatment. Metformin is used frequently in the treatment of patients with diabetes and other illness, but has not yet been used to treat patients with this type of cancer. In this research study, we want to see if using metformin during treatment with chemotherapy and radiation will increase the chance that the cancer will respond to treatment and not return.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 26

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single arm, treatment	Metformin	Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm, experimental treatment consisting of metformin plus chemo-radiation.

Primary Outcome Measures

Name	Time	Method
Phase II - Efficacy (Disease Response Rate)	Treatment duration plus 8-12 weeks following treatment completion (up to 21 weeks total)	Response and progression will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST1.1) Committee \[Eur J Cancer. 2009 Jan; 45(2):228-47\]. Changes in only the largest diameter (uni-dimensional measurement) of the tumor lesions are used in the RECIST 1.1 criteria. For the purposes of this study, patients should be reevaluated for response following completion of treatment as per current institutional protocol for this disease site: 1) spiral contrast enhanced computed tomography (CECT) at 10 weeks following completion of treatment or 2) positron emission tomography (PET) at 12 weeks following completion of treatment. Per RECIST v1.1 criteria for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Disease response rate is defined as the percentage of patients with OR.
Phase I - Dose-Limiting Toxicity	treatment duration plus 30 days following treatment (an average of 13 weeks)	Dose limiting toxicities include diarrhea/gastrointestinal disturbance and hypoglycemia requiring dose reduction, and they will be measured for the time frame detailed above. Adverse Events (AE)s will be graded in accordance with the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE) http://ctep.cancer.gov/ reporting/ctc.html. If not described in the NCI-CTCAE, AEs will be graded according to their severity using the following criteria: grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (life threatening).

Secondary Outcome Measures

Name	Time	Method
Phase II - Progression Free Survival	Date of study registration to recurrence/progression/death or up to 2 years following treatment completion, whichever comes first.	Measurement of time from date of study registration to date of documented radiographic recurrence/progression or death.
Phase II - Overall Survival	Date of study registration to death or up to 2 years following treatment completion, whichever comes first.	Measurement of time from date of study registration to date of death.

Trial Locations

Locations (3): Michael E. DeBakey Veterans Affairs Medical Center
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Houston, Texas, United States
Harris Health System - Smith Clinic
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Houston, Texas, United States
Baylor College of Medicine
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Houston, Texas, United States