Induction Chemotherapy With ACF Followed by Chemoradiation Therapy for Adv. Head & Neck Cancer

Compared to the standard induction regimen of TPF (docetaxel, cisplatin, and 5-FU), the ACCF
(nab-paclitaxel, cisplatin, cetuximab, and 5-FU) regimen included two therapeutic changes:
nab-paclitaxel was substituted for docetaxel and cetuximab was added. The investigators
propose to eliminate cetuximab from the ACCF regimen to isolate the treatment effects of
nab-paclitaxel when given with cisplatin and 5-FU. The primary objective of the ACF proposal
is to determine the complete (CR) rate by clinical examination at the primary tumor site
following two cycles of ACF. An important secondary objective will be to compare the tumor
response rates at the primary site following two cycles of ACF to our historical experience
following two cycles of ACCF (protocol # ABX 218/HRPO# 08-0911). In addition, the
investigators will compare adverse events (AEs) between patients who receive ACF to the
historical group given ACCF. From these two comparisons, we aim to determine if either ACF or
ACCF is superior based on a balance of efficacy (using the surrogate prognostic endpoint of
CR rate at primary tumor site) and toxicity.

Inclusion Criteria:

- Patient must have selected stage III or IVa/b head and neck squamous cell carcinoma
(HNSCC); all patients must have T2-T4 primary tumors; (patients with T1 tumors will be
excluded); although most of these patients will have regional nodal disease, patients
with no nodal disease will also be eligible

- Patient must have disease at the oropharynx, hypopharynx, larynx, or oral cavity
sub-sites

- Patient must have measurable disease defined as lesions that can be accurately
measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with
CT scan

- Patient must be >= 18 years of age.

- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Patient must have adequate bone marrow and organ function as defined below:

- Absolute neutrophil count (ANC) >= 1500/mcL

- Platelets > 100,000/mcL

- Hemoglobin > 9.0 g/dL

- Total bilirubin =< 1.5 mg/dL

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper
limit of normal (ULN)

- Alkaline phosphatase =< 2.5 x ULN

- Serum creatinine < 1.8 mg/dL

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry, for
the duration of study participation, and for 3 months after completing treatment.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she must inform her treating physician immediately

- Patient must be able to understand and willing to sign an Institutional Review Board
(IRB)-approved written informed consent document

- Patient with uncontrolled diabetes or fasting blood glucose level of greater than 200
mg/dL will be eligible for enrollment but will not be evaluable for PET imaging

Exclusion Criteria:

- Patient must not have had prior chemotherapy, prior epidermal growth factor receptor
(EGFR) targeted therapy, or prior radiation therapy for HNSCC

- Patient must not have disease at the nasopharyngeal, sinus, or other sub-site not
specified in the inclusion criteria; patient must not have unknown primary squamous
cell carcinoma of the head and neck

- Patient must not have a history of prior invasive malignancy diagnosed within 3 years
prior to study enrollment other than local stage non-melanoma skin cancer

- Patient must not be receiving any other investigational agents

- Patient must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to any of the agents used in this study

- Patient must not be taking cimetidine or allopurinol. If currently taking either of
these medications, patient must discontinue for one week before receiving treatment
with nab-paclitaxel

- Patient must not have an uncontrolled intercurrent illness including, but not limited
to, ongoing or active serious infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, or serious psychiatric illness/social
situations that would limit compliance with study requirements

- Patient must not be pregnant and/or breastfeeding; a negative serum or urine pregnancy
test is required at screening for all female patients of childbearing potential

- Patient must not be known to be human immunodeficiency virus (HIV)-positive on
combination antiretroviral therapy because of the potential for pharmacokinetic
interactions with the study agents; in addition, these patients are at increased risk
of lethal infections when treated with marrow suppressive therapy; appropriate studies
will be undertaken in patients receiving combination antiretroviral therapy when
indicated

- Patient must not have peripheral neuropathy > grade 1