Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin Followed By Chemoradiation in Treating Patients With Recurrent Head and Neck Cancer

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of
nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) when given in
combination with FHX (5 fluorouracil [fluorouracil], hydroxyurea and twice daily radiation,
in good induction responders) and of nab-paclitaxel added to hypofractionated radiotherapy
for poor responders.

II. To explore the feasibility of a more rapid palliative chemoradiotherapy approach
inpatients with refractory disease as demonstrated by failure to respond to initial
chemotherapy.

III. To explore the role of induction chemotherapy as a predictive tool for definitive head
and neck cancer management of previously treated patients.

SECONDARY OBJECTIVES:

I. Progression-free survival (PFS) (time to disease progression or death from any cause) on
both study arms.

II. Overall survival and response rates in both arms.

TERTIARY OBJECTIVES:

I. To determine the correlation of secreted protein, acidic, cysteine-rich (SPARC)
expression in head and neck cancer and response to therapy.

OUTLINE: This is a dose-escalation study of paclitaxel albumin-stabilized nanoparticle
formulation.

RE-INDUCTION THERAPY (WEEKS 1-6): Patients receive paclitaxel albumin-stabilized
nanoparticle formulation intravenously (IV) over 30 minutes on days 1 and 8 and carboplatin
IV over 30 minutes on day 1. Courses repeat every 21 days for 2 courses in the absence of
disease progression or unacceptable toxicity. Patients achieving good response undergo
surgical resection and proceed to chemoradiation within 4-6 weeks.

AFHX REGIMEN: Patients achieving response to re-induction therapy receive hydroxyurea orally
(PO) every 12 hours for 6 days (11 doses) beginning on day 0, fluorouracil IV continuously
over 120 hours beginning on day 0, and paclitaxel albumin-stabilized nanoparticle
formulation IV over 30 minutes on day 1. Patients also undergo radiation therapy twice daily
(BID) on days 1-5. Courses repeat every 14 days for 5 weeks in the absence of disease
progression or unacceptable toxicity.

PACLITAXEL + RADIATION (AXX) REGIMEN: Patients not achieving response to re-induction
therapy receive paclitaxel albumin-stabilized nanoparticle formulation IV and undergo
hypofractionated radiation therapy on day 1. Courses repeat every 7 days for 5 weeks in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 3 months, every 3
months for 2 years, every 6 months for 2 years, and then yearly thereafter.

Inclusion Criteria:

- Histological or cytological documentation of recurrent head and neck cancer requiring
regional therapy

- Recurrent or second primary, previously irradiated squamous cell carcinoma of the
head and neck (SCCHN) without clinically measurably metastatic disease

- Prior radiation therapy completed >= 4 months, and/or chemotherapy completed >= 1
month before study entry, and patient should have recovered from any adverse effects

- Predominance of disease that is amenable to radiotherapy

- Measurable disease prior to induction chemotherapy

- Eastern Cooperative Oncology Group performance status of one or less

- Life expectancy of greater than 12 weeks

- Women of childbearing potential and sexually active males must use an effective
contraception method during treatment and for three months after completing treatment

- Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at
screening for patients of childbearing potential

- Patients must have < grade 2 pre-existing peripheral neuropathy (per Common
Terminology Criteria for Adverse Events [CTCAE])

- Leukocyte >= 3,000/ul

- Absolute neutrophil count >= 1,500/ul

- Platelets >= 1000,000/ul

- Total bilirubin =< 1.5 x institutional upper limit of normal

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
< 2.5 x institutional upper limit of normal

- Creatinine clearance (CrCl) > 45 mL/min

Exclusion Criteria:

- Previously untreated patients with locoregional-only disease are not eligible

- Patients who have had chemotherapy within 4 weeks prior to entering the study, or
those who have not recovered from adverse events due to agents administered more than
4 weeks earlier

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical composition
agents used in the study

- Patients with pre-existing grade 2 or greater peripheral neuropathy, defined as
sensory alteration or paresthesia (including tingling), interfering with function

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