A Clinical Trial of Endoscopic Surgery Followed by Chemotherapy and Proton Radiation for the Treatment of Tumors in the Sinus and Nasal Passages

Inclusion Criteria:

- Age greater than or equal to 18 years.

- Histopathologically confirmed diagnosis of one the following cancer types:

- Squamous cell carcinoma

- Esthesioneuroblastoma

- Adenoid cystic carcinoma

- Adenocarcinoma

- Paranasal sinus/nasal cavity malignancy is considered unresectable with negative
margins surgery or resection would be considered excessively morbid. This could
include lesions with:

- Carotid involvement

- Cavernous sinus invasion

- Brain invasion

- Orbital apex

- Intraconal space

- Pterygoid musculature involvement

- Invasion of the clivus

- Resection of at least 80% of the volume of the tumor is feasible. Resectability will
be determined by the surgeon and radiologist after discussion among the
multidisciplinary team.

- Patients must be a candidate for surgery (as per treating surgeon) and be able to
tolerate proton radiation and chemotherapy (as per treating radiation oncologist and
medical oncologist).

- Karnofsky performance statue >/= 70

- The subject has organ and marrow function and laboratory values rendering safe
administration of Cisplatin:

- The ANC >/= 1000/mm3 without colony stimulating factor support

- Platelets >/= 100,000/mm3

- Hemoglobin >/= 9 g/dL

- Bilirubin
- Serum albumin >/= 2.8 g/dl

- Creatinine clearance (CrCl) >/= 60 mL/min. For creatinine clearance estimation,
the Cockcroft and Gault equation should be used:

- Male: CrCl (mL/min) = (140 = age) x wt (kg) / (serum creatinine x 72)

- Female: Multiply above result by 0.85

- ALT and AST
- Serum phosphorus, calcium, magnesium and potassium >/= LLN

- No evidence of intercurrent infection

- Negative pregnancy test for women of childbearing potential (<51 years of age) as per
institutional policy.

- Patients with distant metastatic disease may not be included.

- Patient must be able to read and write in English.

- Patients who intitially meet the histopathological inclusion criteria but surgical
pathology report shows Sinonasal Undifferentiated Carcinoma.

Exclusion Criteria:

- Tumor is deemed to be resectable with negative margins by conventional surgical
standards.

- Patients not able to receive standard-dose cisplatin based on the judgement of the
treating medical oncologist.

- Patients with chronic kidney disease (GFR <60), uncontrolled hypertension, congestive
heart failure, pre-existing bone marrow dysfunction, or cytopenias.

° Congestive heart failure (CHF): New York Heart Association (NYHA) Class II-IV at the
time of screening

- Concurrent uncontrolled hypertension defined as sustained blood pressure > 150 mm Hg
systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7
days of the first dose of study treatment; If severe hearing impairment is measured or
if significant neuropathy is reported at baseline the treating physician will discuss
the risks for further permanent hearing loss and neuropathy with the patient.

- Patients not able to have a MRI (due to pacemaker, claustrophobia, etc.).

- Inability to return to MSKCC for frequent scheduled hydration sessions
post-chemotherapy.

- Inability to comply with requirements for cisplatin administration anti-emetic
regimens post-treatment.

- Patients not able or unwilling to travel for proton therapy.