PRIMARY OBJECTIVES:
I. To determine the 2-year progression-free survival (PFS).
SECONDARY OBJECTIVES:
I. Clinical complete response rate (nab-paclitaxel based induction, compared to European
Prospective Investigation into Cancer and Nutrition [EPIC] induction [paclitaxel based]).
II. Response rate (nab-paclitaxel based induction, compared to EPIC induction [paclitaxel
based]).
III. Proportion of patients with >= 50% shrinkage by Response Evaluation Criteria In Solid
Tumors (RECIST) (nab-paclitaxel based induction, compared to EPIC induction, paclitaxel
based).
IV. Toxicity (nab-paclitaxel based induction, compared to EPIC induction [paclitaxel based]).
V. To assess swallowing function and speech at 6 months (mos) and 12 mos post therapy.
VI. To determine the rates of late toxicity with chemoradiation following surgery as
determined by xerostomia, dental decay, osteroradionecrosis, G-tube dependency, tracheostomy
placement and dysphagia.
VII. 2-year overall survival (OS) in patients treated on the Low-Risk, Intermediate-Risk Arm,
and High-Risk Arms.
VIII. 2-year PFS in patients treated on the Low-Risk, Intermediate-Risk Arm, and High-Risk
Arms - early and late toxicities.
IX. Evaluate need for post radiotherapy/chemoradiotherapy (RT/CRT) surgery on low- and
intermediate-risk arms based on response from induction chemotherapy.
X. Evaluate in a descriptive manner the role of transoral robotic surgery (TORS)
resection/lymph node dissection (LND) when integrated into a de-escalation trial.
TERTIARY OBJECTIVES:
I. To evaluate pathologic/histologic appearance of tumor after induction chemotherapy and
after CRT.
II. Translational research on blood and tissue samples. III. To profile tumors genetically
and immunologically in order to assess in a descriptive manner genetic or immunological
features characteristic of clinical behavior.
OUTLINE:
INDUCTION CHEMOTHERAPY: All patients receive paclitaxel albumin-stabilized nanoparticle
formulation intravenously (IV) over 60 minutes on days 1, 8, and 15 and carboplatin IV over
30-60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of
disease progression or unacceptable toxicity.
Patients are then assigned to 1 of 3 treatment groups based on response to induction
chemotherapy.
GROUP A (LOW-DOSE ARM): Patients undergo radiation therapy once daily for 5 weeks.
GROUP B (INTERMEDIATE-DOSE ARM): Patients receive hydroxyurea orally (PO) twice daily (BID)
on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on
day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats
every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
GROUP C (STANDARD-DOSE ARM): Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV
continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive
standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5
courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the principal investigator (PI), patients may receive cisplatin
IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo
daily radiation therapy.
After completion of study treatment, patients are followed up for 30 days, every 3 months for
1 year, every 6 months for 2 years, and then annually for 2 years.
