A Phase II Trial of Cetuximab and Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

The purpose of this study is to determine if the combination of two new drugs, cetuximab (Erbitux) and bevacizumab (Avastin) can increase the effectiveness of treatment for head and neck cancer. Cetuximab has recently been approved by the FDA for head and neck cancer (that is locally or regionally advanced) when used in combination with radiation therapy. Cetuximab is also approved by the FDA for the treatment of colorectal cancer

Eligibility Criteria 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. 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 >20 mm with conventional techniques or as >10 mm with CT scan). RECIST criteria will be used (see section 9). 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. No more than one prior regimen (chemotherapy or biologic/targeted) for recurrent/metastatic disease ECOG performance status of 0-2 (Karnofsky > 60%; see Appendix A). Patients must have normal organ and marrow function as defined below: absolute neutrophil count > 1,000/L platelets > 75,000/L total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) 5 X institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio (see Appendix). For UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be 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. Ability to understand and the willingness to sign a written informed consent document. Pregnant women are excluded from this study because cetuximab and bevacizumab have 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 cetuximab and bevacizumab, breastfeeding should be discontinued if the mother is treated with cetuximab and bevacizumab. The effects of cetuximab and bevacizumab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while in this study, she should inform her treating physician immediately. HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with cetuximab and bevacizumab. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. Inclusion of Women and Minorities Both men and women and members of all ethnic groups are eligible for this trial. The proposed study population is illustrated in the table below. Inclusion of Women in Plan: The gender distribution of our head and neck cancer patients is detailed in the table below. All efforts are made to recruit women patients with head and neck cancer to the University of Pittsburgh Medical Center.