Study 20080008 is a PK sub-study to study 20050251[Japan 20050251A]. All subjects at a limited number of selected sites who are participating in study 20050251[Japan 20050251A] will be asked to participate in this sub-study. The subjects who do not consent to participate in this sub-study may still participate in study 20050251[Japan 20050251A].

This study is designed to estimate the effect of panitumumab on the PK of cisplatin and 5-FU in subjects receiving cisplatin and 5-FU with or without panitumumab.

To maximize any potential effect of panitumumab on the PK of cisplatin and 5-FU, the collection of PK samples of cisplatin and 5-FU will be taken during cycle 2 of the study, the point at which the PK of panitumumab is expected to be at steady-state after a dose of 9 mg/kg given every 3 weeks.

Study Phase: 3 Indication: Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck Primary Objective: To estimate the effect of administration of 9 mg/kg Q3W of panitumumab on the area under the curve (AUC) of total plasma cisplatin-derived platinum levels and the average concentration at steady state (Css) of 5-fluorouracil (5-FU) in subjects who are receiving cisplatin and 5-FU as described in Amgen protocol 20050251[Japan 20050251A].

Secondary Objective(s): To estimate the effect of administration of 9 mg/kg Q3W of panitumumab on the maximum concentration (Cmax) of total plasma cisplatin-derived platinum levels, AUC and Cmax of free plasma cisplatin-derived platinum in subjects who are receiving cisplatin and 5-FU as described in Amgen protocol 20050251[Japan 20050251A].

Hypotheses: This is an estimation sub-study rather than formal hypothesis testing, the following will be estimated:

1. The effect of administration of 9 mg/kg Q3W of panitumumab at steady state on the pharmacokinetics of cisplatin will be estimated based on the ratio for AUC with:without panitumumab of total plasma cisplatin-derived platinum levels. Total plasma cisplatin-derived platinum levels will be the focus since it has been shown in the literature that there are correlations between total plasma cisplatin-derived platinum levels and nephrotoxicity and tumor response (Desoize et al, 1991).
2. The effect of administration of 9 mg/kg Q3W of panitumumab at steady state on the pharmacokinetics of 5-FU assessed based on the average concentration at steady state (Css) of 5-FU.

Study Design: Study 20080008 is a PK sub-study to study 20050251[Japan 20050251A]. All subjects at a limited number of selected sites who are participating in study 20050251[Japan 20050251A] will be asked to participate in this sub-study. The subjects who do not consent to participate in this sub-study may still participate in study 20050251[Japan 20050251A].

This study is designed to estimate the effect of panitumumab on the PK of cisplatin and 5-FU in subjects receiving cisplatin and 5-FU with or without panitumumab.

To maximize any potential effect of panitumumab on the PK of cisplatin and 5-FU, the collection of PK samples of cisplatin and 5-FU will be taken during cycle 2 of the study, the point at which the PK of panitumumab is expected to be at steady-state after a dose of 9 mg/kg given every 3 weeks.

Primary and Secondary Endpoints: The primary endpoints for this study are the ratio of geometric means (with:without panitumumab) for AUC of total plasma cisplatin-derived platinum and average concentration at steady sate (Css) of 5-FU measured at cycle 2 at which time panitumumab levels are anticipated to be at steady state. Secondary endpoints are the ratio of geometric means (with:without panitumumab) for 1) Cmax of total plasma cisplatin-derived platinum and 2) Cmax and AUC of free plasma cisplatin-derived platinum measured at cycle 2.

Sample Size: Approximately 35 subjects from Study 20050251[Japan 20050251A] will participate in Study 20080008. At least fifteen evaluable subjects (defined as providing sufficient PK samples to permit calculation of AUC for total plasma cisplatin-derived platinum and average concentration at steady state for 5-FU in cycle 2) per arm will be required. Additional subjects will be sequentially included until at least fifteen evaluable subjects per arm are achieved. It is therefore estimated that approximately 35 subjects from study 20050251[Japan 20050251A] will need to participate in the sub-study assuming up to 14% of subjects do not provide evaluable data.

• Group 2
  Subjects receiving cisplatin and 5/FU and receiving Panitumumab who have with Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck
  Intervention: Other: Observations
• Group 1
  Subjects receiving cisplatin and 5/FU and not receiving Panitumumab who have with Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck
  Intervention: Other: Observations

Inclusion Criteria:

• Randomized and participating in study 20050251[Japan 20050251A]
• Subject has completed cycle 1 of assigned treatment on study 20050251[Japan 20050251A] at the protocol-specified dose
• Subject planned to receive cycle 2 of treatment (per study 20050251[Japan 20050251A] on day 22 (± 3 days) with no dose reduction, delay, or carboplatin substitution
• Before any sub-study-specific procedures are done, the 20080008 study-specific written informed consent must be obtained

Exclusion Criteria:

• Subject unwilling or unable to comply with requirements of studies 20050251[Japan 20050251A] and 20080008
• Subject previously has entered this study
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures