Recruiting

Phase 2

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

Sponsor:

Mayo Clinic

Code:

NCT06997068

Conditions

Metastatic Oral Cavity Carcinoma

Recurrent Oral Cavity Carcinoma

Stage IVC Lip and Oral Cavity Cancer AJCC v8

Head and Neck Cancer

Hypopharynx Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Celecoxib

Erlotinib Hydrochloride

Imaging Procedure

Interview

Methotrexate

Study Details

Brief summary:

This phase II trial gathers information on the feasibility, safety, and effect of giving methotrexate, erlotinib, and celecoxib in treating head and neck 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 head and neck cancer.

Conditions

Metastatic Oral Cavity Carcinoma

Recurrent Oral Cavity Carcinoma

Stage IVC Lip and Oral Cavity Cancer AJCC v8

Head and Neck Cancer

Hypopharynx Cancer

Study ID

NCT06997068

Start date

Jul 9, 2025

Status verified date

May, 2026

Completion date

Jun 30, 2028

Anticipated

Primary completion date

Jun 30, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Age ≥ 18 years
Histologically confirmed diagnosis of relapsed/metastatic head and neck cancer, including oral cavity, oropharynx \[human papillomavirus (HPV) positive and negative), hypopharynx, and larynx 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

Enrollment

25 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (methotrexate, erlotinib, 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.

Interventions

Celecoxib

Given PO

Erlotinib Hydrochloride

Given PO

Imaging Procedure

Undergo SOC imaging scans

Interview

Ancillary studies

Methotrexate

Given PO

Questionnaire Administration

Ancillary studies

Primary outcome measure

Rates of provider referral and patient enrollment (Feasibility) [ Time Frame: Up to 2 years ]
Rate of retention (Feasibility) [ Time Frame: Up to 2 years ]
Rate of conversion from virtual to in-person visits (Feasibility) [ Time Frame: Up to 2 years ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Katharine A. Price, MD

More Information

Sponsor

Mayo Clinic

Last update posted

May 11, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-05-11.