Conditions: Squamous Cell Carcinoma of Head and Neck
Keywords: PK Study, Metastatic Recurrent
Allocation: RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 67
Healthy volunteers: no

Brief summary:
Study 20080008 was a PK sub-study to study 20050251\[Japan 20050251A\]. This PK protocol was amended 20-March-2009 and is now a Phase 2 stand alone study. There are no sites participating in the U.S.

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.

Detailed description:
Study Phase: 2 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.

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.

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 study.

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 45 subjects 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 45 subjects will need to participate in the study to obtain 30 evauable subjects.

Arms:
arm 1: Subjects receiving cisplatin and 5/FU and receiving Panitumumab who have with Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck arm 2: 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

Interventions: intervention 1: Panitumumab intervention 2: Cisplatin intervention 3: 5FU
Intervention descriptions: intervention 1: This is a PK study comparing Panitumumab plus Chemotherapy to Chemotherapy alone intervention 2: This is a PK study comparing Panitumumab plus Chemotherapy to Chemotherapy alone intervention 3: This is a PK study comparing Panitumumab plus Chemotherapy to Chemotherapy alone

Protocol document: