<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/NCT02245100</url>
  </required_header>
  <id_info>
    <org_study_id>14D.172</org_study_id>
    <secondary_id>2014-010</secondary_id>
    <nct_id>NCT02245100</nct_id>
  </id_info>
  <brief_title>Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer</brief_title>
  <official_title>A Pilot Study to Evaluate the Predictive Value of Circulating Tumor DNA for Clinical Outcome in Patients With Advanced Head and Neck and Lung Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Cancer Center at Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Thomas Jefferson University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot research trial studies circulating tumor deoxyribonucleic acid (DNA) in predicting&#xD;
      outcomes in patients with stage IV head and neck cancer or stage III-IV non-small cell lung&#xD;
      cancer. Studying circulating tumor DNA from patients with head and neck or lung cancer in the&#xD;
      laboratory may help doctors predict how well patients will respond to treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the predictive value of the circulating tumor DNA for disease-free&#xD;
      survival/progression-free survival in patients with advanced head and neck carcinoma (HNC)&#xD;
      and non-small cell lung cancer (NSCLC).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To correlate the levels of plasma tumor DNA with the salivary tumor DNA. II. To correlate&#xD;
      the mutations found in the circulating tumor DNA with the mutations in the tumor tissues.&#xD;
&#xD;
      III. To evaluate the association between presence and absence of circulating tumor DNA&#xD;
      mutation with the tumor burden assessed by using the radiological findings and pre-treatment&#xD;
      fludeoxyglucose (FDG) positron emission tomography (PET)-derived metrics: metabolic tumor&#xD;
      volume (MTV), maximum standardized uptake value (SUVmax), total glycolytic activity (TGA).&#xD;
&#xD;
      IV. To quantify tumor-specific exosomes from plasma. V. To evaluate the utility of&#xD;
      cancer-derived exosomes to serve as prognostic biomarkers for real-time monitoring of&#xD;
      therapeutic efficacy and identifying early recurrence using longitudinal samples from cancer&#xD;
      patients undergoing treatment.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients undergo blood sample collection within 1 month before surgery, radiation therapy, or&#xD;
      chemotherapy; within 1 week after surgical resection (for patients having upfront surgery);&#xD;
      within 1 month before beginning of post-operative radiation therapy (for patients having&#xD;
      upfront surgery); during the second week of radiation therapy, during the last week of&#xD;
      radiation therapy; and at 1 and 3 months after radiation therapy and then every 3 months for&#xD;
      up to 18 months. Patients also undergo saliva sample collection within 1 month before&#xD;
      surgery, radiation therapy, chemoradiation therapy, or system chemotherapy and tissue&#xD;
      collection at the time of surgery (if upfront surgery is indicated). Blood, saliva, and&#xD;
      tissue samples are analyzed for tumor mutations via next generation sequencing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 22, 2014</start_date>
  <completion_date type="Anticipated">December 8, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 8, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Predictive value of circulating tumor DNA for disease-free survival (DFS)/progression-free survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>To evaluate the predictive value of circulating tumor DNA for DFS/PFS, Cox proportional model will be utilized. Circulating tumor DNA will be treated as either continuous or categorical variables in the regression models. The optimal cut-off value to dichotomize the patients by circulating tumor DNA will be determined by time-dependent receiver operating characteristic curve.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between plasma tumor DNA levels and salivary tumor DNA levels</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The correlation between plasma tumor DNA and salivary tumor DNA levels will be modeled through linear regression with least squares approach or using the Spearman correlation coefficient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between absence and presence of circulating tumor DNA mutation with the tumor burden</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Univariate chi-square tests will be used to access the association between absence and presence of circulating tumor DNA mutation with the tumor burden.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between absence and presence of circulating tumor DNA mutation with FDG-PET tumor hypermetabolism status</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Univariate chi-square tests will be used to access the association between absence and presence of circulating tumor DNA mutation with FDG-PET tumor hypermetabolism status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between mutations found in plasma and tissue mutations</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The correlation between mutations found in plasma and tissue mutations will be first explored by univariate chi-square test and then multivariable logistic regression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between circulating tumor cells and circulating tumor DNA</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The correlation between circulating tumor cells and circulating tumor DNA levels will be modeled through linear regression with least squares approach or using the Spearman correlation coefficient.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">130</enrollment>
  <condition>Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma</condition>
  <condition>Salivary Gland Squamous Cell Carcinoma</condition>
  <condition>Stage IIIA Non-small Cell Lung Cancer</condition>
  <condition>Stage IIIB Non-small Cell Lung Cancer</condition>
  <condition>Stage IV Non-small Cell Lung Cancer</condition>
  <condition>Stage IV Squamous Cell Carcinoma of the Hypopharynx</condition>
  <condition>Stage IV Squamous Cell Carcinoma of the Nasopharynx</condition>
  <condition>Stage IVA Salivary Gland Cancer</condition>
  <condition>Stage IVA Squamous Cell Carcinoma of the Larynx</condition>
  <condition>Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity</condition>
  <condition>Stage IVA Squamous Cell Carcinoma of the Oropharynx</condition>
  <condition>Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity</condition>
  <condition>Stage IVA Verrucous Carcinoma of the Larynx</condition>
  <condition>Stage IVA Verrucous Carcinoma of the Oral Cavity</condition>
  <condition>Stage IVB Salivary Gland Cancer</condition>
  <condition>Stage IVB Squamous Cell Carcinoma of the Larynx</condition>
  <condition>Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity</condition>
  <condition>Stage IVB Squamous Cell Carcinoma of the Oropharynx</condition>
  <condition>Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity</condition>
  <condition>Stage IVB Verrucous Carcinoma of the Larynx</condition>
  <condition>Stage IVB Verrucous Carcinoma of the Oral Cavity</condition>
  <condition>Stage IVC Salivary Gland Cancer</condition>
  <condition>Stage IVC Squamous Cell Carcinoma of the Larynx</condition>
  <condition>Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity</condition>
  <condition>Stage IVC Squamous Cell Carcinoma of the Oropharynx</condition>
  <condition>Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity</condition>
  <condition>Stage IVC Verrucous Carcinoma of the Larynx</condition>
  <condition>Stage IVC Verrucous Carcinoma of the Oral Cavity</condition>
  <condition>Tongue Cancer</condition>
  <condition>Untreated Metastatic Squamous Neck Cancer With Occult Primary</condition>
  <arm_group>
    <arm_group_label>Predictive value of circulating DNA</arm_group_label>
    <description>Patients undergo blood sample collection within 1 month before surgery, radiation therapy, or chemotherapy; within 1 week after surgical resection (for patients having upfront surgery); within 1 month before beginning of post-operative radiation therapy (for patients having upfront surgery); during the second week of radiation therapy, during the last week of radiation therapy; and at 1 and 3 months after radiation therapy and then every 3 months for up to 18 months. Patients also undergo saliva sample collection within 1 month before surgery, radiation therapy, chemoradiation therapy, or system chemotherapy and tissue collection at the time of surgery (if upfront surgery is indicated). Blood, saliva, and tissue samples are analyzed for tumor mutations via next generation sequencing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cytology specimen</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Predictive value of circulating DNA</arm_group_label>
    <other_name>Cytologic sampling</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Predictive value of circulating DNA</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood, saliva, and tissue&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients diagnosed with advanced head and neck carcinoma or NSCLC enrolled at Thomas&#xD;
        Jefferson University&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients older than 18 years age&#xD;
&#xD;
          2. Diagnosis of advanced HNC (Stage III, IVA, IVB, IVC) or NSCLC (Stage IIA, IIB, IIIA,&#xD;
             IIIB, IV) (patients with synchronous advanced HNC and NSCLC are eligible)&#xD;
&#xD;
          3. ECOG performance status score of 0-3&#xD;
&#xD;
          4. Life expectancy of 3 months or longer&#xD;
&#xD;
          5. Patients able to provide a written informed consent prior to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior chemotherapy or full course of radiotherapy for their present advanced HNC or&#xD;
             NSCLC&#xD;
&#xD;
          2. Patients are excluded if they have a history of any other malignancy from which the&#xD;
             patient has been disease-free for less than 2 years, with the exception of adequately&#xD;
             treated basal or squamous cell carcinoma of skin&#xD;
&#xD;
          3. Other severe acute or chronic medical or psychiatric condition that may increase the&#xD;
             risk associated with study participation, and in the judgment of the investigator&#xD;
             would make the subject inappropriate for entry into this study&#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>Voichita Bar-Ad, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Thomas Jefferson University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.JeffersonHospital.org</url>
    <description>Jefferson University Hospitals</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>August 4, 2023</last_update_submitted>
  <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Laryngeal Neoplasms</mesh_term>
    <mesh_term>Oropharyngeal Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Verrucous</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Salivary Gland Neoplasms</mesh_term>
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
    <mesh_term>Paranasal Sinus Neoplasms</mesh_term>
    <mesh_term>Neoplasms, Unknown Primary</mesh_term>
    <mesh_term>Tongue Neoplasms</mesh_term>
    <mesh_term>Laryngeal Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT02245100
org study id: 14D.172
secondary id: 2014-010
nct id: NCT02245100
lead sponsor: 
has dmc: Yes
This pilot research trial studies circulating tumor deoxyribonucleic acid (DNA) in predicting
      outcomes in patients with stage IV head and neck cancer or stage III-IV non-small cell lung
      cancer. Studying circulating tumor DNA from patients with head and neck or lung cancer in the
      laboratory may help doctors predict how well patients will respond to treatment.
PRIMARY OBJECTIVES:

      I. To evaluate the predictive value of the circulating tumor DNA for disease-free
      survival/progression-free survival in patients with advanced head and neck carcinoma (HNC)
      and non-small cell lung cancer (NSCLC).

      SECONDARY OBJECTIVES:

      I. To correlate the levels of plasma tumor DNA with the salivary tumor DNA. II. To correlate
      the mutations found in the circulating tumor DNA with the mutations in the tumor tissues.

      III. To evaluate the association between presence and absence of circulating tumor DNA
      mutation with the tumor burden assessed by using the radiological findings and pre-treatment
      fludeoxyglucose (FDG) positron emission tomography (PET)-derived metrics: metabolic tumor
      volume (MTV), maximum standardized uptake value (SUVmax), total glycolytic activity (TGA).

      IV. To quantify tumor-specific exosomes from plasma. V. To evaluate the utility of
      cancer-derived exosomes to serve as prognostic biomarkers for real-time monitoring of
      therapeutic efficacy and identifying early recurrence using longitudinal samples from cancer
      patients undergoing treatment.

      OUTLINE:

      Patients undergo blood sample collection within 1 month before surgery, radiation therapy, or
      chemotherapy; within 1 week after surgical resection (for patients having upfront surgery);
      within 1 month before beginning of post-operative radiation therapy (for patients having
      upfront surgery); during the second week of radiation therapy, during the last week of
      radiation therapy; and at 1 and 3 months after radiation therapy and then every 3 months for
      up to 18 months. Patients also undergo saliva sample collection within 1 month before
      surgery, radiation therapy, chemoradiation therapy, or system chemotherapy and tissue
      collection at the time of surgery (if upfront surgery is indicated). Blood, saliva, and
      tissue samples are analyzed for tumor mutations via next generation sequencing.
observational model: Case-Only
time perspective: Prospective
measure: Predictive value of circulating tumor DNA for disease-free survival (DFS)/progression-free survival (PFS)
time frame: Up to 2 years
description: To evaluate the predictive value of circulating tumor DNA for DFS/PFS, Cox proportional model will be utilized. Circulating tumor DNA will be treated as either continuous or categorical variables in the regression models. The optimal cut-off value to dichotomize the patients by circulating tumor DNA will be determined by time-dependent receiver operating characteristic curve.
measure: Correlation between plasma tumor DNA levels and salivary tumor DNA levels
time frame: Up to 2 years
description: The correlation between plasma tumor DNA and salivary tumor DNA levels will be modeled through linear regression with least squares approach or using the Spearman correlation coefficient.
measure: Association between absence and presence of circulating tumor DNA mutation with the tumor burden
time frame: Up to 2 years
description: Univariate chi-square tests will be used to access the association between absence and presence of circulating tumor DNA mutation with the tumor burden.
measure: Association between absence and presence of circulating tumor DNA mutation with FDG-PET tumor hypermetabolism status
time frame: Up to 2 years
description: Univariate chi-square tests will be used to access the association between absence and presence of circulating tumor DNA mutation with FDG-PET tumor hypermetabolism status.
measure: Correlation between mutations found in plasma and tissue mutations
time frame: Up to 2 years
description: The correlation between mutations found in plasma and tissue mutations will be first explored by univariate chi-square test and then multivariable logistic regression.
measure: Correlation between circulating tumor cells and circulating tumor DNA
time frame: Up to 2 years
description: The correlation between circulating tumor cells and circulating tumor DNA levels will be modeled through linear regression with least squares approach or using the Spearman correlation coefficient.
arm group label: Predictive value of circulating DNA
description: Patients undergo blood sample collection within 1 month before surgery, radiation therapy, or chemotherapy; within 1 week after surgical resection (for patients having upfront surgery); within 1 month before beginning of post-operative radiation therapy (for patients having upfront surgery); during the second week of radiation therapy, during the last week of radiation therapy; and at 1 and 3 months after radiation therapy and then every 3 months for up to 18 months. Patients also undergo saliva sample collection within 1 month before surgery, radiation therapy, chemoradiation therapy, or system chemotherapy and tissue collection at the time of surgery (if upfront surgery is indicated). Blood, saliva, and tissue samples are analyzed for tumor mutations via next generation sequencing.
intervention type: Other
intervention name: Cytology specimen
description: Correlative studies
arm group label: Predictive value of circulating DNA
other name: Cytologic sampling
intervention type: Other
intervention name: Laboratory biomarker analysis
description: Correlative studies
arm group label: Predictive value of circulating DNA
Blood, saliva, and tissue
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Voichita Bar-Ad, MD
role: Principal Investigator
affiliation: Thomas Jefferson University
facility: 
country: United States
url: http://www.JeffersonHospital.org
description: Jefferson University Hospitals
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Carcinoma, Squamous Cell
mesh term: Head and Neck Neoplasms
mesh term: Laryngeal Neoplasms
mesh term: Oropharyngeal Neoplasms
mesh term: Carcinoma, Verrucous
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Salivary Gland Neoplasms
mesh term: Nasopharyngeal Carcinoma
mesh term: Paranasal Sinus Neoplasms
mesh term: Neoplasms, Unknown Primary
mesh term: Tongue Neoplasms
mesh term: Laryngeal Diseases