Methotrexate, Erlotinib, and Celecoxib for the Treatment of Recurrent/Metastatic Oral Cavity Cancer in a Rural Midwest United States Population

Inclusion Criteria:

• Age ≥ 18 years

• Histologically confirmed diagnosis of relapsed/metastatic oral cavity cancer

• Measurable or non-measurable disease is allowed

• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

• Non-measurable disease

• NOTE: Other nonmeasurable lesions include clinically evident lesions notwell visualized on imaging [e.g., oral cavity mass readily seen onphysical exam but obscured on computed tomography (CT)], dermalmetastases, and bone metastases

• Prior treatment:

• One of the following must be true:

• Received standard 1st-line immunotherapy or chemo-immunotherapy OR

• Unable to receive or refuse 1st-line therapy

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2

• Hemoglobin ≥ 9.0 g/dL (obtained 15 days prior to registration)

• Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained 15 days prior to registration)

• Platelet count ≥ 100,000/mm^3 (obtained 15 days prior to registration)

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained 15 days prior toregistration)

• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULNfor patients with liver involvement) (obtained 15 days prior to registration)

• Prothrombin time (PT)/international normalized ratio (INR)/activated partialthromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulanttherapy and INR or aPTT is within target range of therapy (obtained 15 days prior toregistration)

• Calculated creatinine clearance ≥ 45 ml/min per Chronic-Kidney Disease-Epidemiology (CKD-EPI) Creatinine Equation (obtained 15 days prior to registration)

• Estimated creatinine clearance (Clcr) by the CKD-EPI Creatinine Equation (perNational Kidney Foundation) (obtained 15 days prior to registration)

• Negative pregnancy test done ≤ 8 days prior to registration, for persons ofchildbearing potential only

• Provide written informed consent

• Ability to complete questionnaire(s) by themselves or with assistance

• Ability to swallow pills

• Willing and able to adhere with the protocol schedule for the duration of the studyincluding undergoing treatment, attending scheduled visits, and examinations

Exclusion Criteria:

• Any of the following because this study involves an investigational agent, thegenotoxic, mutagenic, and teratogenic effects of which on the developing fetus andnewborn are unknown

• Pregnant persons

• Nursing persons

• Persons of childbearing potential and persons able to father a child who areunwilling to employ adequate contraception

• Uncontrolled intercurrent illness including, but not limited to:

• Myocardial infarction ≤ 6 months prior to registration

• New York Heart Association (NYHA) class III or IV heart failure

• Corrected QT interval (QTc) prolongation more than 440 ms in males and 460 msin females

• Uncontrolled dysrhythmias or poorly controlled angina

• History of serious ventricular arrhythmia [ventricular tachycardia (VT) orventricular flutter (VF)] and/or factors that predispose to arrhythmia (e.g.,heart failure, hypokalemia, family history of long QT syndrome)

• Ongoing or active infection requiring systemic treatment

• Active gastrointestinal bleeding

• Psychiatric illness/social situations that would limit compliance with studyrequirements

• Immunocompromised patients and patients known to be HIV positive and currentlyreceiving antiretroviral therapy

• NOTE: Patients known to be HIV positive, but without clinical evidence of animmunocompromised state, are eligible for this trial

• Known hepatitis

• Exception: For patients with evidence of chronic hepatitis B virus infectionthe hepatitis B (HepB) viral load must be undetectable on suppressive therapy,if indicated, to be eligible

• Exception: Patients with a history of hepatitis C virus infection must havebeen treated and cured. Patients with hepatitis C virus (HCV) infection who arecurrently on treatment are eligible if they have an undetectable HCV viral load

• Receiving any other investigational agent which would be considered as a treatmentfor the primary neoplasm

• Other active malignancy requiring therapy such as radiation, chemotherapy, orimmunotherapy. Patients on hormonal therapy for treated breast or prostate cancerare permitted if they meet other eligibility criteria

• NOTE: Patients with secondary malignancy with life expectancy ≥ 2 years areeligible

• Co-morbid systemic illnesses or other severe concurrent disease which, in thejudgment of the investigator, would make the patient inappropriate for entry intothis study or interfere significantly with the proper assessment of safety andtoxicity of the prescribed regimens