Trial Information

Nab-Paclitaxel-based Re-induction Chemotherapy Followed by Response-stratified Chemoradiotherapy in Patients With Previously Treated Squamous Cell Carcinoma of the Head and Neck.

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.