A Randomized Phase 2 Pharmacokinetic Trial of Chemotherapy With or Without Panitumumab in Patients With Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck

Inclusion Criteria

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck (SCCHN) or its variants (eg, basaloid squamous cell carcinoma and adenosquamous cell carcinoma) of the oral cavity, oropharynx, hypopharynx, or larynx
• Diagnosis of metastatic disease and/or recurrent disease following locoregional therapy and determined to be incurable by surgery or radiotherapy
• Subjects who have received radiation as primary therapy are eligible if locoregional recurrence is in the field of radiation and has occurred ≥6 months after the completion of radiation therapy. Subjects whose locoregional recurrence is solely outside the field of radiation are eligible if the recurrence has occurred ≥ 3 months after the completion of radiation therapy.
• Measurable or non measurable disease. Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to randomization.
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1
• Man or woman ≥ 18 years of age
• Hematological function, as follows (≤ 10 days prior to randomization):

Absolute neutrophil count (ANC) ≥1.5 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL - Renal function, as follows (≤ 10 days prior to randomization):

Creatinine clearance (CrCl) ≥ 50 mL/min calculated by the Cockcroft Gault method as follows:

Male creatinine clearance = (140 age) x (weight in Kg) / (serum Cr x 72) Female creatinine clearance = (140 age) x (weight in Kg) x 0.85 / (serum Cr x 72)

• Hepatic function, as follows (≤ 10 days prior to randomization): Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases) Alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 5 x ULN if liver metastases) Total bilirubin ≤ 1.5 x ULN
• Electrolytes, as follows (≤ 10 days prior to randomization): Magnesium ≥ lower limit of normal (LLN)
• Negative pregnancy test ≤ 72 hours prior to randomization (females of childbearing potential only)

Exclusion Criteria

• Documented or symptomatic central nervous system metastases
• History of another primary cancer, except:

Curatively treated in situ cervical cancer, or Curatively resected non melanoma skin cancer, or Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 2 years prior to randomization

• Subjects whose only site of metastatic disease is a single spiculated lung nodule are assumed to have a second lung primary and are excluded unless there is unequivocal pathological confirmation of metastasis of the SCCHN primary
• Nasopharyngeal carcinoma
• Prior systemic treatment for metastatic and/or recurrent SCCHN Subjects with recurrent disease may have received re irradiation; however subjects who received chemotherapy concomitantly with re irradiation are excluded
• Prior systemic chemotherapy for SCCHN as part of the initial multimodality treatment for locally advanced disease if completed < 6 months prior to randomization
• Prior cisplatin containing induction chemotherapy followed by cisplatin containing chemoradiotherapy
• Prior anti EGFr antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib)
• Subjects requiring immunosuppressive agents (eg, methotrexate and cyclosporine), however corticosteroids are allowed
• Known allergy or hypersensitivity to any component of the study drugs
• Major surgery requiring general anesthesia and a significant incision (ie, larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) ≤ 28 days or minor surgery (excluding central venous catheter placement, percutaneous feeding tube, and biopsy) ≤ 14 days prior to randomization. Subjects must have recovered from surgery related toxicities.
• Clinically significant cardiovascular disease (including myocardial in