Phase I of Biologics and Chemoradiation Therapy for Advanced Head and Neck Cancer

A Phase I Study of the Combination of Chemoradiotherapy With Biologic Therapy for Advanced Head and Neck Cancer

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.

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.