Chemotherapy Before Surgery and Radiation Therapy or Surgery and Radiation Therapy Alone in Treating Patients With Nasal and Paranasal Sinus Cancer That Can Be Removed by Surgery

PRIMARY OBJECTIVES:

I. Evaluate the structure preservation rate for patients with locally advanced resectable
nasal and paranasal sinus squamous cell carcinoma (NPNSCC) with or without neoadjuvant
therapy; all patients will undergo surgical resection and postoperative standard care.

II. Evaluate overall survival (OS) for patients with locally advanced resectable NPNSCC with
or without neoadjuvant therapy followed by surgical resection and postoperative standard
care.

SECONDARY OBJECTIVES:

I. Evaluate progression-free survival (PFS) for this patient population. II. Examine the rate
of structure preservation for the orbit (freedom from orbital exenteration).

III. Evaluate site reported p16 data and correlate with outcome. IV. Determine the accuracy
of baseline/post-chemotherapy magnetic resonance imaging (MRI) and fludeoxyglucose F-18
positron emission tomography/computed tomography (FDG PET/CT)-based prediction of orbit and
skull base preservation.

V. Determine the accuracy of baseline/post-chemotherapy MRI and/or FDG PET/CT-based
prediction of 2-year overall survival.

TERTIARY OBJECTIVES:

I. To determine the effects of tobacco, operationalized as combustible tobacco (1a), other
forms of tobacco (1b), and environmental tobacco exposure (ETS) (1c) on provider-reported
cancer-treatment toxicity (adverse events [both clinical and hematologic] and dose
modifications).

II. To determine the effects of tobacco on patient-reported physical symptoms and
psychological symptoms.

III. To examine quitting behaviors and behavioral counseling/support and cessation medication
utilization.

IV. To explore the effect of tobacco use and exposure on treatment duration, relative dose
intensity, and therapeutic benefit.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients
undergo image guided intensity modulated radiation therapy (IMRT) once daily (QD) for 5
fractions per week for 30 fractions. Patients with positive margins/positive extracapsular
spread (ECS) in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30
fractions and cisplatin intravenously (IV) over 1-2 hours or carboplatin IV over 30 minutes
(for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of
disease progression or unacceptable toxicity.

ARM B: Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1.
Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on
day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease
progression or unacceptable toxicity. Patients then undergo standard of care surgery no later
than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery,
patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients
with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5
fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30
minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if < 2 years
from study entry and then every 6 months if 2-5 years from study entry.

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- General physical condition compatible with the proposed chemotherapy and surgery

- Stage T3 or T4a, histologically-confirmed NPNSCC requiring orbital or skull base
resection:

- Stages T3 and T4a disease will be included regardless of nodal status (N0 or
N1-3), provided that surgical therapy would require orbital or skull base
resection

- The surgical oncologist in each institution will determine the need for resection
of the orbit OR base of skull at baseline for patients on both Arms A and B and
following neo-adjuvant chemotherapy for patients on Arm B

- Resection of skull base will be deemed necessary according to skull base
bone erosion by CT or marrow involvement by MRI is noted; for any disease
abutting the skull base; or for ethmoid sinus or frontal sinus involvement

- Resection of orbital contents will be deemed necessary according to skull
base society guidelines, based on involvement of periorbital fat documented
by MRI imaging

- Patients must be deemed surgically resectable by the surgical teams at each
institution and must have a determination of degree of anticipated structure
preservation of orbit and skull base; this needs to be determined prior to
randomization

- Patients may not be receiving investigational agents at time of registration, or at
any time while on study and during the 4 weeks preceding enrollment

- Patients with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to docetaxel and/or both platinum-based chemotherapy
agents are excluded; patient must be able to receive at least one of the two proposed
chemotherapy regimens

- Patients with evidence of distant metastases or leptomeningeal disease (LMD) are
excluded

- Patients must not have received previous irradiation for head and neck tumor, skull
base, or brain tumors

- Patients with uncontrolled inter-current illnesses which in the opinion of the
investigator will interfere with the ability to undergo therapy including chemotherapy
are excluded

- Patients with a history of a different malignancy are excluded, unless the disease has
not progressed for >= 2 years

- Absolute neutrophil count (ANC) > 1500/mm^3 =< 2 weeks prior to randomization

- Hemoglobin (Hgb) > 8.0 g/dL =< 2 weeks prior to randomization

- Platelet count > 100,000/mm^3 =< 2 weeks prior to randomization

- Creatinine clearance of > 60 ml/min; creatinine clearance may be measured or
calculated; if calculating, creatinine clearance, use the Cockroft-Gault formula =< 2
weeks prior to randomization

- Total bilirubin within normal limits (must be obtained =< 2 weeks prior to
randomization)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) must be within the
range allowing for eligibility, must be obtained < 2 weeks prior to randomization

- Alkaline phosphatase must be within the range allowing for eligibility, must be
obtained < 2 weeks prior to randomization

- Patients with a prior history of squamous cell or basal carcinoma of the skin or in
situ cervical cancer must have been curatively treated

- No current peripheral neuropathy > grade 2 at time of randomization

- Patients must not have any co-existing condition that would preclude full compliance
with the study; no prior history of severe hypersensitivity reaction to docetaxel or
other drugs formulated with polysorbate 80

- Women must not be pregnant or breast-feeding

- All females of childbearing potential must have a blood test or urine study
within 2 weeks prior to registration to rule out pregnancy

- A female of childbearing potential is any woman, regardless of sexual orientation
or whether they have undergone tubal ligation, who meets the following criteria:
1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
naturally postmenopausal for at least 24 consecutive months (i.e., has had menses
at any time in the preceding 24 consecutive months)

- Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception or to abstain from sexual
intercourse for the duration of their participation in the study

- Patients must have measurable disease; MRI and/or PET/CT scans need to be performed
within 2 weeks prior to registration