phase i of biologics and chemoradiation therapy for advanced head and neck cancer

Conditions: Head and Neck Cancer; Parotid Gland Cancer; Thyroid Gland Cancer; Melanoma; Stage IV Head and Neck Cancer

Summary: to determine a safe and effective doses of two biologic drugs, erlotinib and bevacizumab when used with chemotherapy and radiation therapy in advanced head and neck cancer

locally advanced non-operative, stage iv head and neck cancer has at best a guarded prognosis. improvements in outcome have been achieved via the combination of chemotherapy and radiotherapy. concurrent chemoradiotherapy is needed to optimize results, although recent data suggest a benefit from induction therapy as well. nonetheless, despite high remission rates, most of these patients will suffer local-regional and/or distant recurrence from their disease. the proposed study will build upon the framework of chemoradiotherapy (induction plus concurrent) via the addition of a double biologic therapy. specifically, the combination of bevacizumab and erlotinib will be used, as has been studied in other types of cancer.

Eligibility criteria:
inclusion criteria: * locally advanced carcinoma (epithelial malignancy) of the head and neck. this may include non-squamous carcinomas (e.g. parotid, thyroid, melanoma) in which a large portion of mucosa of the oral cavity and/or laryngopharynx is expected to be irradiated. * stage iv disease (t4nany or tanyn2-3). * "oligometastatic" disease is allowable if it is asymptomatic. * measurable disease is not required; patients who have had surgical resection are eligible provided that it is felt that the likelihood of cure with conventional postoperative therapy is \<40% and provided that there will be at least 28 days from the date of surgery to the start of study therapy. * performance status 0-1. * creatinine \< or = 1.5 mg/dl. * anc \> or = 1,800 cells/mm3. * platelets \> or = 150,000 cells/mm3. * hemoglobin \> or = 10 g/dl (transfusion is acceptable if needed). * sgot and/or sgpt \< or = 2.5 times the upper institutional limit of normal. * inr \< or = 2.0. * age \> or = 18 (informed consent). exclusion criteria: * current, recent (within 4 weeks of the day 1, the first infusion of drug in this study) or planned participation in an experimental drug study other than this one. * poorly controlled blood pressure, defined as systolic bp \> 150 and/or diastolic bp \> 100 despite medication. * unstable angina. * ny heart association (nyha) grade ii or greater congestive heart failure. * history of myocardial infarction or stroke within 6 months. * clinically significant peripheral vascular disease. * evidence of bleeding diathesis or coagulopathy. * presence of brain or spinal cord metastases. * major surgical procedure(s), open biopsy or significant traumatic injury within 28 days prior to day 1 (1st day of study treatment) and/or anticipation of need for major surgical procedure during the course of the study. * urine protein: creatinine ratio \> or = 1.0 at screening.\* * carotid artery exposure or other signs of impending carotid artery hemorrhage. * history of abdominal fistula and/or gastrointestinal abdominal abscess within 6 months prior to enrollment. * serious, non-healing wound, ulcer, or bone fracture. * prior irradiation that would result in radiotherapy field "overlap." * requirement for high dose oral anticoagulation (i.e., goal inr \> 2.0). "mini-dose" anticoagulation as may be used to assist in patency of central venous lines is acceptable. subcutaneous low-molecular weight heparin is allowable. * no known allergies to any of the drug therapies being used in this protocol. * no pregnancy, lactation or inability to use medically acceptable birth control if of childbearing potential.

Keywords: head and neck cancer parotid gland cancer thyroid gland cancer melanoma chemoradiotherapy bevacizumab erlotinib