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