| Inclusion Criteria: | 1) Patients must have histologically or cytologically confirmed Squamous Cell Cancer of the Head and neck either (a) metastatic (i.e. American Joint Committee on Cancer Staging System, 6th edition, stage IVC) or (b) recurrent, judged incurable by surgery or radiation.
2) Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/= 20mm with conventional techniques or as >/= 10 mm with CT scan). RECIST criteria will be used.
3) Therapeutic history in conformance with the following: No more than one prior adjuvant/neoadjuvant chemotherapy and/or concomitant chemoradiotherapy regimen that may have included biologic/targeted agent.
4) No more than one prior regimen (chemotherapy or biologic/targeted) for recurrent/metastatic disease.
5) ECOG performance status 0-2 (Karnofsky >/= 60%).
6) Patients must have normal organ and marrow function as defined below: absolute neutrophil count >/= 1,000/microliter; platelets >/= 75,000/microliter; total bilirubin - within normal institutional limits; AST(SGOT)/ALT(SGPT) </=5 X institutional upper limit of normal; creatinine - within normal institutional limits; creatinine clearance >/= 60 mL/min/1.73 meter squared for patients with creatinine levels above institutional normal
7) Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be <1000 mg for patient enrollment. Note: UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. Continued within in inclusion criteria # 8.
8) Continued from inclusion # 7. UPC ratio is calculated using one of the following formula: [urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/Dl. [(urine protein) x 0.088]/[urine creatine] - if urine creatinine is reported in mmol/L
9) All patients should have baseline tumor tissue available for EGFR determination (therapeutic target of cetuximab) and biomarker studies. Patients without available tissue at baseline may undergo tumor biopsy. Patients who provide consent and have accessible tumors will have a repeat biopsy 14 days (an interval between 12-16 days is acceptable) post initiation of therapy. Priority for study entry will be given to patients with easily accessible tumor and who consent to repeat biopsy. Continued in criteria #10.
10) Continuation from criteria #9: Study entry will not be restricted to patients who agree to further biopsies. If a patient enrolls on study and later refuses biopsy (excluding diagnostic), he/she may remain on study.
11) No prior treatment with cetuximab or bevacizumab or other EGFR or VEGF targeting agents.
12) Patients should not have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomyocin C) and biologic/targeted agents within 3 weeks. At least 3 months should have elapsed after prior therapy with monoclonal antibodies.
13) At least 3 weeks should have elapsed from prior radiotherapy.
14) Patients must have no history of gross hemoptysis (defined as bright red blood of a 1/2 teaspoon or more ) or coagulopathy.
15) Patients should not have history of thrombosis (e.g. pulmonary embolism or deep venous thrombosis) and should not be on therapeutic anticoagulation (prophylactic use of warfarin 1 mg per day is allowed) and INR should be less than 1.5 at registration.
16) Patients with history of hypertension must be well-controlled (</=140/90) on a stable regimen of anti-hypertensive therapy.
17) No major surgical procedure, open biospy, or significant traumatic injury within 28 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration. No serious non-healing wound, ulcer, or bone fracture.
18) No unstable angina or myocardial infarction within the previous 6 months; no uncontrolled hypertensive; no symptomatic congestive heart failure; no serious cardiac arrhythmia requiring medication; no clinically significant peripheral vascular disease; no history of any CNS cerebrovascular ischemia or stroke within the last 6 months; no active serious infection.
19) No other coexisting medical condition that would preclude full compliance with the study.
20) Patients may not be receiving any other investigational agents.
21) Patients should not have a history of prior severe infusion reaction to a monoclonal antibody. Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies.
22) No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 3-year disease-free interval.
23) Age >/= 18 years. Because no dosing or adverse event data are currently available on the use of cetuximab and bevacizumab in patients < 18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
24) Ability to understand and the willingness to sign a written informed consent document.
25) Inclusion of Women in Plan: All efforts are made to recruit women patients with head and neck cancer.
26) Inclusion of Minorities Plan: All efforts are made to recruit minorities with head and neck cancer to receive treatment.
27) Inclusion of Children Plan: It will be assured that individuals under the age of 21 will be enrolled in the study. However, the mean age of the squamous cell carcinoma of the head and neck is between 52 and 56. Therefore, patients under 21 will be rare, and not many patients under this age expected to participate in the phase I clinical trial. |