A Clinical Trial of Endoscopic Surgery Followed by Chemotherapy and Proton Radiation for the Treatment of Tumors in the Sinus and Nasal Passages
Condition: Paranasal Sinus Cancer; Nasal Cavity Tumor; Nasal Cavity Adenocarcinoma
MeSH terms: Adenocarcinoma; Paranasal Sinus Neoplasms
Intervention: Cisplatin; Adjuvant Proton Radiotherapy; Endoscopic Resection; cisplatin and etoposide
Intervention description: Cisplatin should be administered on day 1 (+/- 3 days) of the start of radiotherapy and then every 3 weeks (unless there is a delay for safety concerns such as neutropenia) for a total of 3 cycles. 100 mg/m^2 (dose reductions after the first cycle allowed for toxicity); Proton therapy treatment will follow the National Cancer Institute's "Guidelines for the Use of Proton Radiation Therapy in NCI-Sponsored Cooperative Group Trials". Proton therapy techniques may include passively scattered or scanning or pencil beam technology.; In brief, an endoscope is used and two surgeons perform the intervention in a binostril manner. Tumor is generally resected with an emphasis on identification of the attachments in the paranasal sinuses, nasal cavity, or skull base.; If the final surgical pathology report shows SNUC, at the discretion of the treating medical oncologist, the patient will receive an addition of etoposide chemotherapy to cisplatin chemotherapy. The dose of cisplatin will be decresed from 100 mg/m2 to 60 mg/m2. Cisplatin should be administered on days 1-2, 21-22 and 42-43 at a dose of 60 mg/m2 and Etoposide should be administered at days 1-3, 21-23, and 42-44 at a dose of 120 mg/m2.
Intervention MeSH terms: Cisplatin; Etoposide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: squamous cell carcinoma; esthesioneuroblastoma; adenoid cystic carcinoma; adenocarcinoma; cisplatin; 17-442

Summary:

      This study is being done to test a new treatment plan for large tumors in the sinus or nasal
      cavity that will include endoscopic surgery plus chemotherapy and proton-beam radiation
      therapy.
    

Eligibility criteria:

        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. For patients who have had surgery at an outside institution,
             the same parameters will be thoroughly screened to ensure the patient met the same
             inclusion criteria and resection standards.

          -  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 </= 1.5 mg/dL the ULM. For subjects with Gilbert's disease, bilirubin
                  </= 3.0 mg/dL

               -  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 </= 3.0 ULN

               -  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.