<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/NCT03829722</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2018.085</org_study_id>
    <secondary_id>HUM00154941</secondary_id>
    <nct_id>NCT03829722</nct_id>
  </id_info>
  <brief_title>Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-related Head and Neck Cancer</brief_title>
  <official_title>Phase II Trial of Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-Related Oropharynx Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan Rogel 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>
      The purpose of this study is to find out if the addition of nivolumab can improve 2 year&#xD;
      progression free survival (PFS) as compared to standard of care of fractionated radiation&#xD;
      therapy (RT) and carboplatin/paclitaxel in subjects with high risk HPV-related squamous cell&#xD;
      carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate).&#xD;
      Fractionated means the radiation will be administered in fragments or parts across multiple&#xD;
      days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 5, 2019</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</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>Progression-free survival (PFS)</measure>
    <time_frame>Up to 2 years after completion of study treatment</time_frame>
    <description>Estimated using the Kaplan-Meier method. Evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who progressed in any location</measure>
    <time_frame>Up to 2 years after completion of study treatment</time_frame>
    <description>To characterize patterns of failure, investigators will summarize the proportion of patients who progressed in any location and whether the first progression was local, regional, distant or in multiple locations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 2 years after completion of study treatment</time_frame>
    <description>Estimated using the Kaplan-Meier method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of acute toxicity</measure>
    <time_frame>Up to 6 months after completion of study treatment</time_frame>
    <description>Toxicity evaluation per CTCAE v 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of late toxicity</measure>
    <time_frame>Up to 2 years after completion of study treatment</time_frame>
    <description>Toxicity evaluation per CTCAE v 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of mid-treatment FDG-PET scans with post-treatment PET-CT.</measure>
    <time_frame>12 weeks after completion of study treatment</time_frame>
    <description>Correlation of metabolic image uptake data on mid-treatment FDG-PET scans performed between fractions 8-12 with standard 12 week post-treatment PET-CT.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Oropharynx Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Nivolumab, Carboplatin/Paclitaxel, Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Therapy will continue for 21 weeks total. This includes 4 doses of of nivolumab (240mg/m2) before and concurrent with RT/carboplatin/paclitaxel and 4 adjuvant nivolumab doses (480mg/m2) after the end of RT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Given intravenously (IV), 240 mg every 2 weeks for 4 doses concurrent with radiation therapy (RT). Following completion of RT, 480 mg given every 4 weeks for 4 doses.</description>
    <arm_group_label>Nivolumab, Carboplatin/Paclitaxel, Radiotherapy</arm_group_label>
    <other_name>Opdivo</other_name>
    <other_name>BMS-936558</other_name>
    <other_name>MDX1106</other_name>
    <other_name>ONO-4538</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Given IV once per week during radiation therapy (AUC=1).</description>
    <arm_group_label>Nivolumab, Carboplatin/Paclitaxel, Radiotherapy</arm_group_label>
    <other_name>Paraplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Given IV once per week during radiation therapy (30mg/m^2)</description>
    <arm_group_label>Nivolumab, Carboplatin/Paclitaxel, Radiotherapy</arm_group_label>
    <other_name>Taxol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Given 5 days/week for a total of 35 doses (70 gray total).</description>
    <arm_group_label>Nivolumab, Carboplatin/Paclitaxel, Radiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Histologically or cytologically proven squamous cell carcinoma of the oropharynx&#xD;
             (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by&#xD;
             immunohistochemistry or HPV positive by in situ hybridization&#xD;
&#xD;
          -  Clinical stage: stage III AJCC 8th edition staging (cT4 or cN3) OR &quot;matted lymph&#xD;
             nodes&quot; (defined as 3 LNs abutting one another with loss of intervening fat plane that&#xD;
             is replaced with evidence of extracapsular spread)&#xD;
&#xD;
          -  Appropriate stage for protocol entry, including no distant metastases, based upon the&#xD;
             following minimum diagnostic workup:&#xD;
&#xD;
               -  History/physical examination, including documentation of weight within 2 weeks&#xD;
                  prior to registration;&#xD;
&#xD;
               -  FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration;&#xD;
                  Zubrod Performance Status 0-1 within 2 weeks prior to registration;&#xD;
&#xD;
               -  Age ≥ 18;&#xD;
&#xD;
          -  CBC/differential obtained within 2 weeks prior to registration on study, with adequate&#xD;
             bone marrow function defined as follows:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3; Platelets ≥ 75,000 cells/mm3;&#xD;
                  Hemoglobin ≥ 9.0 g/dL AST/ALT &lt;3 x ULN&#xD;
&#xD;
               -  Total Bilirubin &lt;1.5 x ULN (except subjects with Gilbert Syndrome who must have a&#xD;
                  total bilirubin level &lt; 3 x ULN)&#xD;
&#xD;
          -  Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45&#xD;
             mL/min within 2 weeks prior to registration;&#xD;
&#xD;
          -  Women of childbearing potential must agree to use a medically effective means of birth&#xD;
             control throughout their participation in the treatment phase of the study and for&#xD;
             five months after the last treatment. A woman of childbearing potential (WOCBP) is&#xD;
             defined as any female who has experienced menarche and who has not undergone surgical&#xD;
             sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal.&#xD;
             Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the&#xD;
             absence of other biological or physiological causes. In addition, females under the&#xD;
             age of 55 years must have a serum follicle stimulating hormone (FSH) level &gt; 40 mIU/mL&#xD;
             to confirm menopause. Men receiving nivolumab who are sexually active with WOCBP must&#xD;
             agree to use effective contraception throughout their participation in the treatment&#xD;
             phase of the study and for seven months after the last treatment.&#xD;
&#xD;
          -  Due to the potential for serious adverse reactions in breastfed infants from&#xD;
             carboplatin/paclitaxel and nivolumab, women are advised not to breast-feed during&#xD;
             treatment with carboplatin/paclitaxel or nivolumab&#xD;
&#xD;
          -  The patient must provide study-specific informed consent prior to study entry.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity,&#xD;
             or cervix are all permissible);&#xD;
&#xD;
          -  Any prior therapy for the study cancer; note that prior chemotherapy for a different&#xD;
             cancer is allowable if &gt; 3 years prior to study;&#xD;
&#xD;
          -  Any history of active autoimmune disease that has required systemic treatment in the&#xD;
             past 2 years (i.e., with use of disease modifying agents, corticosteroids or&#xD;
             immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic&#xD;
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is&#xD;
             not considered a form of systemic treatment.&#xD;
&#xD;
          -  Prior radiotherapy to the region of the study cancer that would result in overlap of&#xD;
             radiation therapy fields;&#xD;
&#xD;
          -  Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               -  Unstable angina and/or congestive heart failure requiring hospitalization within&#xD;
                  the last 6 months;&#xD;
&#xD;
               -  Uncontrolled diarrhea;&#xD;
&#xD;
               -  Uncontrolled adrenal insufficiency;&#xD;
&#xD;
               -  Transmural myocardial infarction within the last 3 months;&#xD;
&#xD;
               -  Acute bacterial or fungal infection requiring systemic antibiotics at the time of&#xD;
                  registration;&#xD;
&#xD;
               -  Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory&#xD;
                  illness requiring hospitalization or precluding study therapy at the time of&#xD;
                  registration;&#xD;
&#xD;
               -  Acquired Immune Deficiency Syndrome (AIDS) with CD4+ count &lt; 350 cells per&#xD;
                  microL; note, however, that HIV testing is not required for entry into this&#xD;
                  protocol. The need to exclude patients with AIDS from this protocol is necessary&#xD;
                  because the treatments involved in this protocol may be significantly&#xD;
                  immunosuppressive.&#xD;
&#xD;
          -  Pregnancy or women of childbearing potential and men who are sexually active and not&#xD;
             willing/able to use contraception; this exclusion is necessary because the treatment&#xD;
             involved in this study may be significantly teratogenic.&#xD;
&#xD;
          -  Women who are breastfeeding and are not willing to discontinue breastfeeding during&#xD;
             the trial&#xD;
&#xD;
          -  Poorly controlled diabetes (defined as fasting glucose level &gt; 200 mg/dL) despite 2&#xD;
             attempts to improve glucose control by fasting duration and adjustment of medications.&#xD;
             Patients with diabetes will preferably be scheduled in the morning and instructions&#xD;
             for fasting and use of medications will be provided in consultation with the patients'&#xD;
             primary physicians&#xD;
&#xD;
          -  Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other&#xD;
             form of immunosuppressive therapy within 7 days prior to the first dose of trial&#xD;
             treatment. Short bursts of steroids of 5-7 days (for COPD exacerbation or other&#xD;
             similar indication) are allowed.&#xD;
&#xD;
          -  Known history of, or any evidence of active, non-infectious pneumonitis.&#xD;
&#xD;
          -  Known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
          -  Hypersensitivity to nivolumab or any of its excipients or known hypersensitivity to&#xD;
             carboplatin/paclitaxel.&#xD;
&#xD;
          -  Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
          -  Received a live vaccine within 30 days of planned start of study therapy.&#xD;
&#xD;
          -  Have any condition that, in the opinion of the investigator, would compromise the&#xD;
             well-being of the subject or the study or prevent the subject from meeting or&#xD;
             performing study requirements&#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>Michelle Mierzwa, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Rogel Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>December 20, 2022</last_update_submitted>
  <last_update_submitted_qc>December 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2022</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, Squamous Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Nivolumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03829722
org study id: UMCC 2018.085
secondary id: HUM00154941
nct id: NCT03829722
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to find out if the addition of nivolumab can improve 2 year
      progression free survival (PFS) as compared to standard of care of fractionated radiation
      therapy (RT) and carboplatin/paclitaxel in subjects with high risk HPV-related squamous cell
      carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate).
      Fractionated means the radiation will be administered in fragments or parts across multiple
      days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival (PFS)
time frame: Up to 2 years after completion of study treatment
description: Estimated using the Kaplan-Meier method. Evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
measure: Proportion of patients who progressed in any location
time frame: Up to 2 years after completion of study treatment
description: To characterize patterns of failure, investigators will summarize the proportion of patients who progressed in any location and whether the first progression was local, regional, distant or in multiple locations.
measure: Overall survival (OS)
time frame: Up to 2 years after completion of study treatment
description: Estimated using the Kaplan-Meier method
measure: Incidence of acute toxicity
time frame: Up to 6 months after completion of study treatment
description: Toxicity evaluation per CTCAE v 5.0
measure: Incidence of late toxicity
time frame: Up to 2 years after completion of study treatment
description: Toxicity evaluation per CTCAE v 5.0
measure: Correlation of mid-treatment FDG-PET scans with post-treatment PET-CT.
time frame: 12 weeks after completion of study treatment
description: Correlation of metabolic image uptake data on mid-treatment FDG-PET scans performed between fractions 8-12 with standard 12 week post-treatment PET-CT.
arm group label: Nivolumab, Carboplatin/Paclitaxel, Radiotherapy
arm group type: Experimental
description: Therapy will continue for 21 weeks total. This includes 4 doses of of nivolumab (240mg/m2) before and concurrent with RT/carboplatin/paclitaxel and 4 adjuvant nivolumab doses (480mg/m2) after the end of RT.
intervention type: Drug
intervention name: Nivolumab
description: Given intravenously (IV), 240 mg every 2 weeks for 4 doses concurrent with radiation therapy (RT). Following completion of RT, 480 mg given every 4 weeks for 4 doses.
arm group label: Nivolumab, Carboplatin/Paclitaxel, Radiotherapy
other name: Opdivo
other name: BMS-936558
other name: MDX1106
other name: ONO-4538
intervention type: Drug
intervention name: Carboplatin
description: Given IV once per week during radiation therapy (AUC=1).
arm group label: Nivolumab, Carboplatin/Paclitaxel, Radiotherapy
other name: Paraplatin
intervention type: Drug
intervention name: Paclitaxel
description: Given IV once per week during radiation therapy (30mg/m^2)
arm group label: Nivolumab, Carboplatin/Paclitaxel, Radiotherapy
other name: Taxol
intervention type: Radiation
intervention name: Radiation Therapy
description: Given 5 days/week for a total of 35 doses (70 gray total).
arm group label: Nivolumab, Carboplatin/Paclitaxel, Radiotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michelle Mierzwa, M.D.
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Squamous Cell
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Nivolumab
sharing ipd: No