Study of Combination Chemotherapy Treatment for Head and Neck Cancer

Inclusion Criteria

• CRITERIA FOR SCREENING BIOPSY: Age >= 18 years. Because no dosing or adverse event data are currently available on the use of imatinib in combination with CTX in patients < 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
• CRITERIA FOR SCREENING BIOPSY: Subjects must have suspected or known clinical presentation of head and neck squamous cell carcinoma (HNSCC) or a recurrence of HNSCC after initial therapy. For newly suspected head and neck cancer, the procedure will obtain tissue for both standard of care biopsy and additional tissue for research.
• CRITERIA FOR SCREENING BIOPSY: Participants must have sufficient tumor volume (approximately 10 cc) to accommodate 2 research biopsies (at minimum 2-3 core samples for each biopsy taken at baseline and post imatinib plus CTX therapy). The amount of sufficient tumor volume will be determined by the treating physician. This will be approximated based on clinical evidence, such as physician visualization or palpitation.
• CRITERIA FOR SCREENING BIOPSY: Surgical management or definitive radiation therapy (+/- concurrent chemotherapy) must be the chosen modality for management of the head and neck squamous cell cancer.
• CRITERIA FOR SCREENING BIOPSY: Informed consent: subjects must be informed of the investigational nature of the study and must be able to sign a written informed consent.
• CRITERIA FOR SCREENING BIOPSY: Subjects with a medical history of human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy with undetectable viral load within 6 months to be eligible for this trial.
• CRITERIA FOR SCREENING BIOPSY: Subjects with a medical history of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load while on suppressive therapy, if indicated.
• CRITERIA FOR SCREENING BIOPSY: Subjects with a medical history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load while on suppressive therapy, if indicated.
• CRITERIA FOR SCREENING BIOPSY: Subjects with a history of brain metastases, new or progressive brain metastases, or leptomeningeal disease are not eligible for this trial.
• CRITERIA FOR SCREENING BIOPSY: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• CRITERIA FOR SCREENING BIOPSY: Subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• CRITERIA FOR SCREENING BIOPSY: Subjects who have evidence of distant metastatic disease are eligible for this clinical trial as long as the treatment of the locoregional disease is deemed as taking precedence over treatment of the remaining systemic disease.
• CRITERIA FOR TREATMENT: Histological confirmation of squamous cell carcinoma of the head and neck.
• CRITERIA FOR TREATMENT: For those patients with oropharyngeal cancer, subjects must have either: * Human papillomavirus (HPV)-negative status by p16 expression or HPV-deoxyribonucleic acid (DNA) expression. * HPV-positive status by p16 expression AND a > 10 pack year smoking history.
• CRITERIA FOR TREATMENT: Eastern Cooperate Oncology Group (ECOG) performance status =< 1 within 30 days prior to registration.
• CRITERIA FOR TREATMENT: Leukocytes >= 3,000/mcL.
• CRITERIA FOR TREATMENT: Absolute neutrophil count >= 1,000/mcL.
• CRITERIA FOR TREATMENT: Platelets >= 100,000/mcL.
• CRITERIA FOR TREATMENT: Total bilirubin =< institutional upper limit of normal (ULN).
• CRITERIA FOR TREATMENT: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN.
• CRITERIA FOR TREATMENT: Creatinine =< 1.5 x institutional ULN.
• CRITERIA FOR TREATMENT: Subjects of childbearing potential must not be pregnant (confirmed by a negative urine/serum pregnancy test within 7 days of treatment). NOTE: Subjects are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. A medically acceptable method of birth control must be used such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for 6 months after last dose of study drugs. Subjects who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be of childbearing potential.
• CRITERIA FOR TREATMENT: Subjects who are not surgically or medically sterile must agree to use an acceptable method of contraception. Subjects who have partners that are pregnant, possibly pregnant, or who could become pregnant must agree to use a medically acceptable method of birth control such as an oral, implantable, injectable, or other transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream) during the study and for 6 months post study drugs. Total abstinence for the same study period is an acceptable alternative.

Exclusion Criteria

• Subjects with a diagnosis of nasopharyngeal carcinoma, advanced cutaneous squamous cell carcinoma of the head and neck, or salivary gland tumors are excluded from this study.
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
• Prior chemotherapy, radiotherapy, or major surgery within 8 weeks of study enrollment or those who have not recovered (to grade =< 1 or baseline) from clinically significant adverse events due to agents administered more than 8 weeks earlier (alopecia and fatigue excluded). Clinical significance to be determined by the study investigator.
• Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Subjects who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib or CTX.
• Subjects with uncontrolled intercurrent illness.
• Subjects with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant subjects are excluded from this study because imatinib and CTX are agents 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 imatinib plus CTX, breastfeeding should be discontinued if the mother is treated with imatinib plus CTX. The projected duration starts with the screening visit through 6 months after the last dose of trial treatment.
• Prior imatinib is allowed as long as the last treatment dose was administered >= 8 weeks prior to the first study dose of imatinib plus CTX.
• Prior CTX therapy is allowed as long as the last treatment dose was administered >= 8 weeks prior to the first study dose of imatinib plus CTX.
• Any of the following cardiac conditions: * Uncontrolled or poorly-controlled arrhythmia or uncontrolled cardiac insufficiency. * Uncontrolled or poorly-controlled hypertension (>180 mmHg systolic or > 130 mmHg diastolic).
• Any of the following conditions: * History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 28 days of study enrollment. * History of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study enrollment. * History of myocardial infarction, ventricular arrhythmia, stable/unstable angina, symptomatic congestive heart failure, coronary/peripheral artery bypass graft or stenting or other significant cardiac disease within 6 months prior to study enrollment. * History of arterial or venous thrombosis/thromboembolic event, including pulmonary embolism within 6 months of study enrollment. * Use of herbal supplements (St. John’s Wort, gingko biloba, etc.) within one week of imatinib plus CTX treatment.