Inclusion Criteria:

• Histologically or cytologically confirmed squamous cell carcinoma of head and neck (SCCHN) of oropharynx, oral cavity, hypopharynx, or larynx with at least 1 measurable lesion using CT or MRI scan
• Diagnosis of recurrent disease determined to be incurable by surgery or radiotherapy
• Karnofsky Performance Status (KPS) score ≥ 60% at screening
• Men or women age ≥18 years
• Adequate hematologic, electrolyte and hepatic functions and negative pregnancy test

Exclusion Criteria:

• Subject received > 1 chemotherapy regimen for the treatment of metastatic or recurrent disease
• Concomitant chemotherapy for recurrent disease administered solely for the purpose of radiation sensitization during re-irradiation will not be counted towards this chemotherapy regimen
• Nasopharyngeal carcinoma, salivary gland and primary skin SCCHN, or symptomatic central nervous system (CNS) metastases
• History of interstitial lung disease, significant cardiovascular disease, or another primary cancer
• Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection
• Known allergy or hypersensitivity to any component of panitumumab
• Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, panitumumab, cetuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib) for recurrent or metastatic disease with the following exceptions: - Prior EGFr inhibitor therapy is allowed if received as part of prior multimodality treatment (eg, as radiation sensitizer) and completed > 24 weeks prior to randomization
• Subjects who received no more than one dose of cetuximab and discontinued prior to progression due to documented severe infusion reaction are eligible.
• Significant thromboembolic event ≤ 8 weeks prior to enrollment
• Subjects not recovered from all previous acute radiotherapy-related toxicities
• History of severe skin disorder that in the opinion of the investigator may interfere with study conduct
• History of any medical, or psychiatric condition, or laboratory abnormality that may interfere with the interpretation of study results
• Subject is currently in a clinical trial ≤ 30 days prior to enrollment
• Subjects requiring use of immunosuppressive agents however corticosteroids are allowed
• Man or woman of child-bearing potential who do not consent to use adequate contraceptive precautions during the course of the study
• Female subject who is pregnant or breast-feeding
• Subject requiring major surgery using general/spinal anesthesia ≤ 28 days prior to enrollment, or minor surgery ≤ 14 days prior to enrollment.