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

Phase 2

Not yet recruiting

• Conditions: Metastatic Oral Cavity Carcinoma; Stage IVC Lip and Oral Cavity Cancer AJCC v8; Recurrent Oral Cavity Carcinoma
• Interventions: Drug: Celecoxib; Drug: Erlotinib Hydrochloride; Procedure: Imaging Procedure; Other: Interview; Drug: Methotrexate; Other: Questionnaire Administration

• Registration Number: NCT06997068
• Lead Sponsor: Mayo Clinic

Brief Summary

This phase II trial gathers information on the feasibility, safety, and effect of giving methotrexate, erlotinib, and celecoxib in treating oral cavity cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic) among rural Midwest patients. Methotrexate is in a class of medications called antimetabolites. It is also a type of antifolate. Methotrexate stops cells from using folic acid to make deoxyribonucleic acid and may kill tumor cells. Erlotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving the combination of methotrexate, erlotinib, and celecoxib may be feasible, safe, and effective in treating rural Midwest patients with recurrent/metastatic oral cavity cancer.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-21
• Study First Submitted QC: 2025-05-21
• Last Update Submitted: 2025-05-21
• Study First Posted: 2025-05-30
• Last Update Posted: 2025-05-30
• Study Start: 2025-06-19
• Primary Completion: 2028-06-30
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 25

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 not well visualized on imaging [e.g., oral cavity mass readily seen on physical exam but obscured on computed tomography (CT)], dermal metastases, 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 to registration)

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

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

• 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 (per National Kidney Foundation) (obtained 15 days prior to registration)

• Negative pregnancy test done ≤ 8 days prior to registration, for persons of childbearing 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 study including undergoing treatment, attending scheduled visits, and examinations

Exclusion Criteria

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

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential and persons able to father a child who are unwilling 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 ms in females
  • Uncontrolled dysrhythmias or poorly controlled angina
  • History of serious ventricular arrhythmia [ventricular tachycardia (VT) or ventricular 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 study requirements

• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy

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

• Known hepatitis

  • Exception: For patients with evidence of chronic hepatitis B virus infection the 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 have been treated and cured. Patients with hepatitis C virus (HCV) infection who are currently on treatment are eligible if they have an undetectable HCV viral load

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

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

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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (methotrexate, erlotinib, celecoxib)	Celecoxib	Patients receive methotrexate PO on days 1, 8, 15, and 22 of each cycle, erlotinib PO QD on days 1-28 of each cycle, and celecoxib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SOC imaging scans throughout the trial.
Treatment (methotrexate, erlotinib, celecoxib)	Erlotinib Hydrochloride	Patients receive methotrexate PO on days 1, 8, 15, and 22 of each cycle, erlotinib PO QD on days 1-28 of each cycle, and celecoxib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SOC imaging scans throughout the trial.
Treatment (methotrexate, erlotinib, celecoxib)	Imaging Procedure	Patients receive methotrexate PO on days 1, 8, 15, and 22 of each cycle, erlotinib PO QD on days 1-28 of each cycle, and celecoxib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SOC imaging scans throughout the trial.
Treatment (methotrexate, erlotinib, celecoxib)	Interview	Patients receive methotrexate PO on days 1, 8, 15, and 22 of each cycle, erlotinib PO QD on days 1-28 of each cycle, and celecoxib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SOC imaging scans throughout the trial.
Treatment (methotrexate, erlotinib, celecoxib)	Methotrexate	Patients receive methotrexate PO on days 1, 8, 15, and 22 of each cycle, erlotinib PO QD on days 1-28 of each cycle, and celecoxib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SOC imaging scans throughout the trial.
Treatment (methotrexate, erlotinib, celecoxib)	Questionnaire Administration	Patients receive methotrexate PO on days 1, 8, 15, and 22 of each cycle, erlotinib PO QD on days 1-28 of each cycle, and celecoxib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SOC imaging scans throughout the trial.

Primary Outcome Measures

Name	Time	Method
Rates of provider referral and patient enrollment (Feasibility)	Up to 2 years	Will capture the provider/patient reasons for declining trial participation. All information will be described descriptively. Categorical variables will be described with frequencies and percentages. Continuous variables will be described with means, medians, standard deviations, etc.
Rate of retention (Feasibility)	Up to 2 years	Will capture the reasons for trial drop-out and assess adherence to treatment and reasons for deviation through qualitative and semiquantitative means. All information will be described descriptively. Categorical variables will be described with frequencies and percentages. Continuous variables will be described with means, medians, standard deviations, etc.
Rate of conversion from virtual to in-person visits (Feasibility)	Up to 2 years	Will capture the provider/patient reasons for the switch and quantify the out-of-pocket costs of in-person and virtual visits. All the information will be described descriptively. Categorical variables will be described with frequencies and percentages. Continuous variables will be described with means, medians, standard deviations, etc.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	Up to 3 years	Defined as the time from study entry until the first of either disease progression or death from any cause.
Overall survival	Up to 3 years	Defined as the time from study entry until death from any cause.
Incidence of adverse events	Up to 30 days after completion of study treatment	The maximum grade for each type of adverse event will be recorded for each patient, assessed per Common Terminology Criteria in Adverse Events (CTCAE) version 5.0.
Objective response rate	Up to 3 years	Defined as the proportion of participants who have a partial response or complete response, as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States