Clinical Trials /

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

NCT02949700

Description:

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.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Study OF Metformin in Combination With Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma
  • Official Title: A Phase I/II Study OF Metformin in Combination With Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: H-39773
  • NCT ID: NCT02949700

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
MetforminSingle arm, treatment

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Single arm, treatmentExperimentalPatients 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.
  • Metformin

Eligibility Criteria

        INCLUSION CRITERIA:

          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. Only patients with HPV- disease will be
             included in the Phase II component of the study; HPV status will be ascertained using
             the currently utilized clinical standard of p16 overexpression via
             immunohistochemistry.

          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.

               1. Myelosuppressive chemotherapy: Must not have received within 4 weeks of
                  enrollment onto this study (6 weeks if prior nitrosourea).

               2. Hematopoietic growth factors: At least 7 days since the completion of therapy
                  with a growth factor.

               3. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy
                  with a biologic agent.

               4. Monoclonal Antibody: At least 6 weeks must have elapsed since prior therapy that
                  includes a monoclonal antibody.

               5. 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.

               6. 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.

               7. Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and
                  >/= 2 months must have elapsed since transplant.

          4. 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.

          5. Performance Status: ECOG performance status less than or equal to 3.

          6. 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

          7. 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.

          8. Informed Consent: Ability to understand and the willingness to sign a written informed
             consent document.

        EXCLUSION CRITERIA:

          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: Pregnant women are excluded from this study because metformin is a US FDA
             class B agent with the potential for teratogenic or abortifacient effects. Because
             there is an unknown but potential risk for adverse events in nursing infants secondary
             to treatment of the mother with metformin, breastfeeding should be discontinued if the
             mother is treated with metformin.

          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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I - toxicity
Time Frame:treatment duration plus 30 days following treatment
Safety Issue:
Description: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) 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).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Baylor College of Medicine

Trial Keywords

  • metformin
  • head and neck cancer

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