<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03274414</url>
  </required_header>
  <id_info>
    <org_study_id>17-442</org_study_id>
    <nct_id>NCT03274414</nct_id>
  </id_info>
  <brief_title>A Clinical Trial of Endoscopic Surgery Followed by Chemotherapy and Proton Radiation for the Treatment of Tumors in the Sinus and Nasal Passages</brief_title>
  <official_title>A Phase II, Single-Arm Trial Assessing Local Control of Near Total Endoscopic Resection Followed by Concurrent Chemotherapy and Proton Radiation in the Treatment of Unresectable Sinonasal Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being done to test a new treatment plan for large tumors in the sinus or nasal&#xD;
      cavity that will include endoscopic surgery plus chemotherapy and proton-beam radiation&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">January 13, 2023</completion_date>
  <primary_completion_date type="Actual">January 13, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Local control assessment of unresectable paranasal sinus and nasal cavity tumors</measure>
    <time_frame>1 year</time_frame>
    <description>Assessment of local control after near-total endoscopic resection (NTR) followed by concurrent chemotherapy with proton-beam radiation in unresectable tumors (which we define as expected inability to perform negative margin surgery) of the paranasal sinuses and nasal cavity.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Paranasal Sinus Cancer</condition>
  <condition>Nasal Cavity Tumor</condition>
  <condition>Nasal Cavity Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Unresectable paranasal sinus/nasal cavity malignancy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <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)</description>
    <arm_group_label>Unresectable paranasal sinus/nasal cavity malignancy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Adjuvant Proton Radiotherapy</intervention_name>
    <description>Proton therapy treatment will follow the National Cancer Institute's &quot;Guidelines for the Use of Proton Radiation Therapy in NCI-Sponsored Cooperative Group Trials&quot;. Proton therapy techniques may include passively scattered or scanning or pencil beam technology.</description>
    <arm_group_label>Unresectable paranasal sinus/nasal cavity malignancy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endoscopic Resection</intervention_name>
    <description>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.</description>
    <arm_group_label>Unresectable paranasal sinus/nasal cavity malignancy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cisplatin and etoposide</intervention_name>
    <description>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.</description>
    <arm_group_label>Unresectable paranasal sinus/nasal cavity malignancy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater than or equal to 18 years.&#xD;
&#xD;
          -  Histopathologically confirmed diagnosis of one the following cancer types:&#xD;
&#xD;
               -  Squamous cell carcinoma&#xD;
&#xD;
               -  Esthesioneuroblastoma&#xD;
&#xD;
               -  Adenoid cystic carcinoma&#xD;
&#xD;
               -  Adenocarcinoma&#xD;
&#xD;
          -  Paranasal sinus/nasal cavity malignancy is considered unresectable with negative&#xD;
             margins surgery or resection would be considered excessively morbid. This could&#xD;
             include lesions with:&#xD;
&#xD;
               -  Carotid involvement&#xD;
&#xD;
               -  Cavernous sinus invasion&#xD;
&#xD;
               -  Brain invasion&#xD;
&#xD;
               -  Orbital apex&#xD;
&#xD;
               -  Intraconal space&#xD;
&#xD;
               -  Pterygoid musculature involvement&#xD;
&#xD;
               -  Invasion of the clivus&#xD;
&#xD;
          -  Resection of at least 80% of the volume of the tumor is feasible. Resectability will&#xD;
             be determined by the surgeon and radiologist after discussion among the&#xD;
             multidisciplinary team. For patients who have had surgery at an outside institution,&#xD;
             the same parameters will be thoroughly screened to ensure the patient met the same&#xD;
             inclusion criteria and resection standards.&#xD;
&#xD;
          -  Patients must be a candidate for surgery (as per treating surgeon) and be able to&#xD;
             tolerate proton radiation and chemotherapy (as per treating radiation oncologist and&#xD;
             medical oncologist).&#xD;
&#xD;
          -  Karnofsky performance statue &gt;/= 70&#xD;
&#xD;
          -  The subject has organ and marrow function and laboratory values rendering safe&#xD;
             administration of Cisplatin:&#xD;
&#xD;
               -  The ANC &gt;/= 1000/mm3 without colony stimulating factor support&#xD;
&#xD;
               -  Platelets &gt;/= 100,000/mm3&#xD;
&#xD;
               -  Hemoglobin &gt;/= 9 g/dL&#xD;
&#xD;
               -  Bilirubin &lt;/= 1.5 mg/dL the ULM. For subjects with Gilbert's disease, bilirubin&#xD;
                  &lt;/= 3.0 mg/dL&#xD;
&#xD;
               -  Serum albumin &gt;/= 2.8 g/dl&#xD;
&#xD;
               -  Creatinine clearance (CrCl) &gt;/= 60 mL/min. For creatinine clearance estimation,&#xD;
                  the Cockcroft and Gault equation should be used:&#xD;
&#xD;
               -  Male: CrCl (mL/min) = (140 = age) x wt (kg) / (serum creatinine x 72)&#xD;
&#xD;
               -  Female: Multiply above result by 0.85&#xD;
&#xD;
               -  ALT and AST &lt;/= 3.0 ULN&#xD;
&#xD;
               -  Serum phosphorus, calcium, magnesium and potassium &gt;/= LLN&#xD;
&#xD;
          -  No evidence of intercurrent infection&#xD;
&#xD;
          -  Negative pregnancy test for women of childbearing potential (&lt;51 years of age) as per&#xD;
             institutional policy.&#xD;
&#xD;
          -  Patients with distant metastatic disease may not be included.&#xD;
&#xD;
          -  Patient must be able to read and write in English.&#xD;
&#xD;
          -  Patients who intitially meet the histopathological inclusion criteria but surgical&#xD;
             pathology report shows Sinonasal Undifferentiated Carcinoma.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Tumor is deemed to be resectable with negative margins by conventional surgical&#xD;
             standards.&#xD;
&#xD;
          -  Patients not able to receive standard-dose cisplatin based on the judgement of the&#xD;
             treating medical oncologist.&#xD;
&#xD;
          -  Patients with chronic kidney disease (GFR &lt;60), uncontrolled hypertension, congestive&#xD;
             heart failure, pre-existing bone marrow dysfunction, or cytopenias.&#xD;
&#xD;
             ° Congestive heart failure (CHF): New York Heart Association (NYHA) Class II-IV at the&#xD;
             time of screening&#xD;
&#xD;
          -  Concurrent uncontrolled hypertension defined as sustained blood pressure &gt; 150 mm Hg&#xD;
             systolic or &gt; 100 mm Hg diastolic despite optimal antihypertensive treatment within 7&#xD;
             days of the first dose of study treatment; If severe hearing impairment is measured or&#xD;
             if significant neuropathy is reported at baseline the treating physician will discuss&#xD;
             the risks for further permanent hearing loss and neuropathy with the patient.&#xD;
&#xD;
          -  Patients not able to have a MRI (due to pacemaker, claustrophobia, etc.).&#xD;
&#xD;
          -  Inability to return to MSKCC for frequent scheduled hydration sessions&#xD;
             post-chemotherapy.&#xD;
&#xD;
          -  Inability to comply with requirements for cisplatin administration anti-emetic&#xD;
             regimens post-treatment.&#xD;
&#xD;
          -  Patients not able or unwilling to travel for proton therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc Cohen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memoral Sloan Kettering Basking Ridge</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memoral Sloan Kettering Monmouth</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memoral Sloan Kettering Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>January 17, 2023</last_update_submitted>
  <last_update_submitted_qc>January 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>squamous cell carcinoma</keyword>
  <keyword>esthesioneuroblastoma</keyword>
  <keyword>adenoid cystic carcinoma</keyword>
  <keyword>adenocarcinoma</keyword>
  <keyword>cisplatin</keyword>
  <keyword>17-442</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Paranasal Sinus Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03274414
org study id: 17-442
nct id: NCT03274414
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Local control assessment of unresectable paranasal sinus and nasal cavity tumors
time frame: 1 year
description: Assessment of local control after near-total endoscopic resection (NTR) followed by concurrent chemotherapy with proton-beam radiation in unresectable tumors (which we define as expected inability to perform negative margin surgery) of the paranasal sinuses and nasal cavity.
arm group label: Unresectable paranasal sinus/nasal cavity malignancy
arm group type: Experimental
intervention type: Drug
intervention name: Cisplatin
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)
arm group label: Unresectable paranasal sinus/nasal cavity malignancy
intervention type: Radiation
intervention name: Adjuvant Proton Radiotherapy
description: 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.
arm group label: Unresectable paranasal sinus/nasal cavity malignancy
intervention type: Procedure
intervention name: Endoscopic Resection
description: 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.
arm group label: Unresectable paranasal sinus/nasal cavity malignancy
intervention type: Drug
intervention name: cisplatin and etoposide
description: 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.
arm group label: Unresectable paranasal sinus/nasal cavity malignancy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Cohen, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Paranasal Sinus Neoplasms
mesh term: Cisplatin
mesh term: Etoposide
sharing ipd: Undecided