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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02949700
Recruitment Status : Active, not recruiting
First Posted : October 31, 2016
Last Update Posted : February 25, 2021
Information provided by (Responsible Party):
Vlad Sandulache, 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.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: Metformin Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study OF Metformin in Combination With Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : January 26, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Single arm, treatment

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.

Drug: Metformin
Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation.

Primary Outcome Measures :
  1. Phase I - toxicity [ Time Frame: treatment duration plus 30 days following treatment ]
    Metformin associated toxicities include diarrhea and gastrointestinal disturbance and 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) 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).

  2. Phase II - efficacy [ Time Frame: Treatment duration plus 2 years following treatment completion ]
    We will measure disease response rate for patients in the trial and compare this outcome with matched historical controls. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  1. Diagnosis: Patients must have histologically or cytologically confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx or larynx. Patients eligible for inclusion must have stage III-IV SCC of the above sites based on current AJCC clinical and imaging based staging (see Appendix A for staging criteria). For the phase II component, patients should present with: 1) HPV- SCC or 2) HPV+ SCC and a concomitant ≥10pack-year smoking history documented in the clinical record; HPV status will be ascertained using the currently utilized clinical standard of p16 overexpression via immunohistochemistry for all patients. Immunohistochemistry to determine p16 overexpression is only a requirement for oropharyngeal disease.
  2. Disease Status: Only patients with active, measurable disease will be included in the study.
  3. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Patients treated with chemotherapy (i.e. cisplatin) and/or EBRT for a cancer at a different, non-head and neck site, will be eligible for the trial. Patients previously treated with chemotherapy and/or EBRT for a cancer of the head and neck region, irrespective of histology will not be eligible to participate in the trial.
  4. Myelosuppressive chemotherapy: Must not have received within 4 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
  5. Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor.
  6. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.
  7. Monoclonal Antibody: At least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody.

    Other: For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.

  8. XRT: >/= 14days for local palliative XRT (small port); >/= 90days must have elapsed if prior TBI, craniospinal XRT or if >/= 50% radiation of pelvis; >/= 45days must have elapsed if other substantial bone marrow radiation.
  9. Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and >/= 2 months must have elapsed since transplant.
  10. Age: Patients must be >/=18 years of age. Because no dosing or adverse event data are currently available on the use of metformin in cancer patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
  11. Performance Status: ECOG performance status less than or equal to 3.
  12. Organ Function: Patients must have normal organ and marrow function as defined below:

    1. leukocytes >/= 3,000/mcL
    2. absolute neutrophil count >/= 1,500/mcL
    3. platelets >/= 100,000/mcL
    4. total bilirubin within normal institutional limits
    5. AST(SGOT) </= 2.5X institutional upper limit of normal
    6. creatinine < 1.5mg/dL OR
    7. creatinine clearance >/= 60 mL/min/1.73 m2 for patients with creatinine levels > institutional normal
  13. Patients must be candidates for standard of care treatment consisting of chemotherapy (cisplatin) and radiation.
  14. Willingness to Use Contraception: The effects of metformin on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  15. Informed Consent: Ability to understand and the willingness to sign a written informed consent document.


  1. Concomitant Medications: Patients may not be receiving any other investigational agents.
  2. Brain metastases: Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  3. Prior Allergies: History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin.
  4. Patients with diabetes mellitus (DM) will be excluded from the study. Criteria for a diagnosis of diabetes mellitus are as follows: a) known diagnosis of DM, b) active treatment for DM, c) fasting glucose level ≥ 126mg/dl or d) hemoglobin A1c ≥ 6.0% obtained within 30 days prior to registration.
  5. Intercurrent Illness: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  6. Pregnancy: Patients may not be pregnant or breastfeeding.
  7. HIV: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with metformin. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  8. Patients taking metformin for any reason will not be eligible for inclusion in the study.
  9. Patients may not have been treated for another SCC of the oral cavity, oropharynx, hypopharynx or larynx in the past.

Information from the National Library of Medicine

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 identifier (NCT number): NCT02949700

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United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Michael E. DeBakey Veterans Affairs Medical Center
Houston, Texas, United States, 77030
Harris Health System - Smith Clinic
Houston, Texas, United States, 77054
Sponsors and Collaborators
Baylor College of Medicine
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Principal Investigator: Vlad Sandulache, MD, PhD Baylor College of Medicine
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Responsible Party: Vlad Sandulache, Assistant Professor, Baylor College of Medicine Identifier: NCT02949700    
Other Study ID Numbers: H-39773
First Posted: October 31, 2016    Key Record Dates
Last Update Posted: February 25, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Vlad Sandulache, Baylor College of Medicine:
head and neck cancer
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Hypoglycemic Agents
Physiological Effects of Drugs