Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer

Pathologically staged squamous cell carcinoma of the head and neck, stage III or IVa (AJCC
6th edition 2002) of the oral cavity, larynx, or hypopharynx that is status post potentially
curative surgical resection without gross residual tumor, except the following: a)T3N0
laryngeal primary and b) any T1N1, if there are no high-risk pathologic features (high risk
defined as positive margins, extracapsular spread, and perineural or angiolymphatic
invasion). Patients should not have gross residual disease. No prior chemotherapy,
biologic/targeted therapy (including any prior therapy which specifically and directly
targets the EGFR pathway), or radiotherapy for head and neck cancer. A brief course, up to 2
weeks, of prior neoadjuvant single-agent biologic/targeted therapy of any type (except EGFR
monoclonal antibodies) prior to surgical resection is permitted. No more than 7 weeks
(minimum of 3 weeks) should have elapsed between surgery and initiation of radiation. No
prior radiation or chemotherapy for head and neck cancer. ECOG performance status of 0-1.
Patients must have normal organ and marrow function as defined below: absolute neutrophil
count >=1,500/mL; Platelets >=100,000/mL; Hemoglobin >=10 g/dL; Total bilirubin 1.5 x normal
institutional limits; Creatinine clearance > 60 ml/min. No prior invasive malignancy unless
the DFS is 3 years or more. Age >= 18 years. Pregnant or breast-feeding women are excluded
(see exclusion criteria). Informed consent must be obtained from all patients prior to
beginning therapy. Patients should have the ability to understand and the willingness to sign
a written informed consent document. Patients who have tumor tissue available from previous
diagnostic or therapeutic procedures should submit the specimen for assessment of EGFR and
related biomarkers after signing informed consent. In-Eligibility: Uncontrolled intercurrent
illness including, but not limited to, ongoing or active infection or psychiatric
illness/social situations that would limit compliance with study requirements. Significant
history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina,
recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure,
and cardiomyopathy with decreased ejection fraction. All patients will have a baseline EKG.
If abnormalities consistent with active coronary artery disease are detected, the patient
will be referred to a cardiologist for appropriate evaluation and management prior to
treatment on study. Patients with history of hypertension must be well-controlled upon study
entry (≤150/90) on a stable regimen of anti-hypertensive therapy. Patients should not have
any prior history of hypertensive crisis or hypertensive encephalopathy.Patients may not be
receiving any other investigational agents. No history of prior malignancy, with the
exception of curatively treated squamous cell or basal carcinoma of the skin or in situ
cervical cancer, or malignancy that has been treated with a curative intent with a 3-year
disease-free survival. No patients with significant baseline sensory or motor neurologic
deficits (> grade I neuropathy) will be treated on this study. Pregnant women are excluded
from this study because chemotherapy and radiation therapy 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 chemotherapy, breastfeeding
should be discontinued if the mother is treated with chemotherapy. Prior to study enrollment,
women of childbearing potential (WOCBP) must be advised of the importance of avoiding
pregnancy during trial participation and the potential risk factors for an unintentional
pregnancy. In addition, men enrolled on this study should understand the risks to any sexual
partner of childbearing potential and should practice an effective method of birth control.
All WOCBP MUST have a negative urine pregnancy test at baseline, or within 7 days prior to
receiving investigational product. The minimum sensitivity of the pregnancy test must be 25
IU/L or equivalent units of HCG. If the urine pregnancy test is positive, a serum pregnancy
test will then be performed to confirm the result. In the event that both the urine and serum
pregnancy tests are positive, the subject must not receive investigational product and must
not be enrolled in the study. In addition, all WOCBP should be instructed to contact the
Investigator immediately if they suspect they might be pregnant (e.g., missed or late
menstrual period) at any time during study participation. The Investigator must immediately
notify Amgen in the event of a confirmed pregnancy in a patient participating in the study.
Prior severe infusion reaction to a human monoclonal antibody.Prior severe infusion reaction
to a human monoclonal antibody.

Inclusion Criteria:

- Pathologically staged squamous cell carcinoma of the head and neck, stage III or IVa
(AJCC 6th edition 2002) of the oral cavity, larynx, or hypopharynx that is status post
potentially curative surgical resection without gross residual tumor, except the
following: a)T3N0 laryngeal primary and b) any T1N1, if there are no high-risk
pathologic features (high risk defined as positive margins, extracapsular spread, and
perineural or angiolymphatic invasion).

- Patients should not have gross residual disease.

- No prior chemotherapy, biologic/targeted therapy (including any prior therapy which
specifically and directly targets the EGFR pathway), or radiotherapy for head and neck
cancer. A brief course, up to 2 weeks, of prior neoadjuvant single-agent
biologic/targeted therapy of any type (except EGFR monoclonal antibodies) prior to
surgical resection is permitted.

- No more than 6 7 weeks (minimum of 3 weeks) should have elapsed between surgery and
initiation of radiation.

- No prior radiation or chemotherapy for head and neck cancer.

- ECOG performance status of 0-1

- Patients must have normal organ and marrow function Absolute neutrophil count
>/=1,500/uL Platelets >/=100,000/uL Hemoglobin >/= 10 g/dL Total bilirubin <1.5 x
normal institutional limits Creatinine clearance > 60 mL/min

- No prior invasive malignancy unless the DFS is 3 years or more.

- Age > 18 years.

- Pregnant or breast-feeding women are excluded (see exclusion criteria).

- Informed consent must be obtained from all patients prior to beginning therapy.
Patients should have the ability to understand and the willingness to sign a written
informed consent document.

- Patients who have tumor tissue available from previous diagnostic or therapeutic
procedures should submit the specimen for assessment of EGFR and related biomarkers
after signing informed consent.

Exclusion Criteria:

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements. Significant history of uncontrolled cardiac disease; i.e.,
uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior
6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased
ejection fraction. All patients will have a baseline EKG. If abnormalities consistent
with active coronary artery disease are detected, the patient will be referred to a
cardiologist for appropriate evaluation and management prior to treatment on study..
Patients with history of hypertension must be well-controlled upon study entry
(≤150/90) on a stable regimen of anti-hypertensive therapy. Patients should not have
any prior history of hypertensive crisis or hypertensive encephalopathy.

- Patients may not be receiving any other investigational agents.

- No history of prior malignancy, with the exception of curatively treated squamous cell
or basal carcinoma of the skin or in situ cervical cancer, or malignancy that has been
treated with a curative intent with a 3-year disease-free survival.

- No patients with significant baseline sensory or motor neurologic deficits(> grade I
neuropathy) will be treated on this study.

- Pregnant women are excluded from this study because chemotherapy and radiation therapy
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 chemotherapy, breastfeeding should be discontinued if the
mother is treated with chemotherapy.

- Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of
the importance of avoiding pregnancy during trial participation and the potential risk
factors for an unintentional pregnancy. In addition, men enrolled on this study should
understand the risks to any sexual partner of childbearing potential and should
practice an effective method of birth control.

- All WOCBP MUST have a negative urine pregnancy test at baseline, or within 7 days
prior to receiving investigational product. The minimum sensitivity of the pregnancy
test must be 25 IU/L or equivalent units of HCG. If the urine pregnancy test is
positive, a serum pregnancy test will then be performed to confirm the result. In the
event that both the urine and serum pregnancy tests are positive, the subject must not
receive investigational product and must not be enrolled in the study.

- In addition, all WOCBP should be instructed to contact the Investigator immediately if
they suspect they might be pregnant (e.g., missed or late menstrual period) at any
time during study participation.

The Investigator must immediately notify Amgen in the event of a confirmed pregnancy in a
patient participating in the study.

-Prior severe infusion reaction to a human monoclonal antibody.