<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/NCT03829007</url>
  </required_header>
  <id_info>
    <org_study_id>PINCH</org_study_id>
    <nct_id>NCT03829007</nct_id>
  </id_info>
  <brief_title>PD-L1 ImagiNg to prediCt Durvalumab Treatment Response in HNSCC</brief_title>
  <acronym>PINCH</acronym>
  <official_title>PINCH - PD-L1 ImagiNg to prediCt Durvalumab Treatment Response in HNSCC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Non-invasive imaging of tumor PD-L1 expression with 89Zr-labeled durvalumab PET/CT predicts&#xD;
      response to durvalumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The programmed death 1 (PD1)/ programmed death ligand 1 (PD-L1) pathway plays an important&#xD;
      role in regulating the T-cell anti tumor response. Blocking this interaction with the anti&#xD;
      PD-L1 monoclonal antibody durvalumab has proven to be effective resulting in durable disease&#xD;
      control rates. Currently, PD-L1 expression as determined by immune histochemistry (IH) is the&#xD;
      best available biomarker for treatment response, but standardized scoring criteria are&#xD;
      lacking and the risk for sampling errors exists. Molecular imaging using 89Zr-labeled&#xD;
      antibodies may overcome these limitations, enabling the visualization of PD-L1 expression in&#xD;
      primary and metastatic tumor lesions and providing information on the in vivo accessibility&#xD;
      of the PD-L1 target following intravenous administration. Besides, a baseline FDG-PET scan&#xD;
      will be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 15, 2019</start_date>
  <completion_date type="Actual">December 9, 2021</completion_date>
  <primary_completion_date type="Actual">December 17, 2020</primary_completion_date>
  <phase>Phase 1/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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tumor uptake of 89Zr-durvalumab</measure>
    <time_frame>1 year</time_frame>
    <description>standardized uptake values (SUV) of 89Zr-durvalumab uptake in tumor lesions will be measured.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess the potential of PD-L1 PET imaging to predict disease control rate of patients with recurrent or advanced head and neck cancer treated with durvalumab q4w 1500mg iv</measure>
    <time_frame>1-2 year</time_frame>
    <description>PD-L1 PET imaging performed with the optimal dose as assessed in part 1 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between tumor uptake of 89Zr-durvalumab and PD-L1 expression as determined immunohistochemically</measure>
    <time_frame>1-2 years</time_frame>
    <description>PD-L1 expression performed by Ventana SP263</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>PD-L1 imaging</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>89Zr-durvalumab iv injection followed by a PET/CT scan at day 5 after injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>PD-L1 imaging</intervention_name>
    <description>89Zr-durvalumab injection followed by a PET/CT scan 5 days after injection</description>
    <arm_group_label>PD-L1 imaging</arm_group_label>
    <other_name>89Zr-durvalumab PET/CT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab treatment is initiated after the PET/CT scan in a fixed dose of 1500 mg iv q4w</description>
    <arm_group_label>PD-L1 imaging</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent and any locally-required authorization (e.g., HIPAA in the&#xD;
             USA, EU Data Privacy Directive in the EU) obtained from the subject prior to&#xD;
             performing any protocol-related procedures, including screening evaluations&#xD;
&#xD;
          2. Age &gt; 18 years at time of study entry, age &gt; 20 years for Japanese subjects.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          4. Life expectancy of &gt; 12 weeks&#xD;
&#xD;
          5. Adequate normal organ and marrow function as defined below:&#xD;
&#xD;
               1. Hemoglobin≥ 9.0 mmol/L&#xD;
&#xD;
               2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (&gt; 1500 per mm3)&#xD;
&#xD;
               3. Platelet count ≥ 100 x 109/L (&gt;100,000 per mm3)&#xD;
&#xD;
               4. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (This will not&#xD;
                  apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent&#xD;
                  hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis&#xD;
                  or hepatic pathology), who will be allowed only in consultation with their&#xD;
                  physician)&#xD;
&#xD;
               5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver&#xD;
                  metastases are present, in which case it must be ≤ 5x ULN&#xD;
&#xD;
               6. Serum creatinine CL&gt;40 mL/min by MDRD&#xD;
&#xD;
          6. Female subjects must either be of non-reproductive potential (i.e., post-menopausal by&#xD;
             history: ≥60 years old and no menses for ≥1 year without an alternative medical cause;&#xD;
             OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of&#xD;
             bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.&#xD;
&#xD;
          7. Subject is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations including follow&#xD;
             up.&#xD;
&#xD;
          8. Histological proven recurrent or metastatic squamous cell cancer of the head and neck&#xD;
&#xD;
          9. At least one lesion with a tumor size ≥1 cm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             staff and/or staff at the study site). Previous enrollment in the present study&#xD;
&#xD;
          2. Participation in another clinical study with an investigational product during the&#xD;
             last 4 weeks&#xD;
&#xD;
          3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab&#xD;
&#xD;
          4. History of another primary malignancy except for:&#xD;
&#xD;
               -  Malignancy treated with curative intent and with no known active disease ≥5 years&#xD;
                  before the first dose of study drug and of low potential risk for recurrence&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease&#xD;
&#xD;
               -  Adequately treated carcinoma in situ without evidence of disease e.g., cervical&#xD;
                  cancer in situ&#xD;
&#xD;
          5. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,&#xD;
             endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal&#xD;
             antibodies, other investigational agent) 28 days prior to the first dose of study drug&#xD;
             28 days prior to the first dose of study drug for subjects who have received prior&#xD;
             TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or&#xD;
             mitomycin C).&#xD;
&#xD;
          6. Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3&#xD;
             electrocardiograms (ECGs) using Frediricia's Correction&#xD;
&#xD;
          7. Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or&#xD;
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of&#xD;
             prednisone, or an equivalent corticosteroid&#xD;
&#xD;
          8. Any unresolved toxicity (&gt;CTCAE grade 2) from previous anti-cancer therapy. Subjects&#xD;
             with irreversible toxicity that is not reasonably expected to be exacerbated by the&#xD;
             investigational product may be included (e.g., hearing loss, peripherally neuropathy)&#xD;
&#xD;
          9. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous&#xD;
             immunotherapy agent, or any unresolved irAE &gt;Grade 1&#xD;
&#xD;
         10. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects&#xD;
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within&#xD;
             the past 2 years) are not excluded.&#xD;
&#xD;
         11. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,&#xD;
             ulcerative colitis)&#xD;
&#xD;
         12. History of primary immunodeficiency&#xD;
&#xD;
         13. History of allogeneic organ transplant&#xD;
&#xD;
         14. History of hypersensitivity to durvalumab or any excipients&#xD;
&#xD;
         15. History of hypersensitivity to the combination or comparator agent (If applicable)&#xD;
&#xD;
         16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active&#xD;
             bleeding diatheses including any subject known to have evidence of acute or chronic&#xD;
             hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirements or&#xD;
             compromise the ability of the subject to give written informed consent&#xD;
&#xD;
         17. Active infection including tuberculosis (clinical evaluation that includes clinical&#xD;
             history, physical examination and radiographic findings, and TB testing in line with&#xD;
             local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),&#xD;
             hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients&#xD;
             with a past or resolved HBV infection (defined as the presence of hepatitis B core&#xD;
             antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for&#xD;
             hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative&#xD;
             for HCV RNA.&#xD;
&#xD;
         18. History of leptomeningeal carcinomatosis&#xD;
&#xD;
         19. Receipt of live attenuated vaccination within 30 days prior to study entry or within&#xD;
             30 days of receiving durvalumab&#xD;
&#xD;
         20. Female subjects who are pregnant, breast-feeding or male or female patients of&#xD;
             reproductive potential who are not employing an effective method of birth control:&#xD;
             Female patient of child-bearing potential&#xD;
&#xD;
               -  Females of childbearing potential who are sexually active with a non sterilized&#xD;
                  male partner must use at least 1 highly effective method of contraception (Table&#xD;
                  1) from the time of screening and must agree to continue using such precautions&#xD;
                  for 180 days after the last dose of durvalumab + tremelimumab combination therapy&#xD;
                  or 90 days after the last dose of durvalumab monotherapy (based on 5x the&#xD;
                  half-life of durvalumab or tremelimumab). Non-sterilized male partners of a&#xD;
                  female patient must use male condom plus spermicide throughout this period.&#xD;
                  Cessation of birth control after this point should be discussed with a&#xD;
                  responsible physician. Not engaging in sexual activity for the total duration of&#xD;
                  the drug treatment and the drug washout period is an acceptable practice;&#xD;
                  however, periodic abstinence, the rhythm method, and the withdrawal method are&#xD;
                  not acceptable methods of birth control. Female patients should also refrain from&#xD;
                  breastfeeding throughout this period.&#xD;
&#xD;
               -  Male patients with a female partner of childbearing potential. Non-sterilized&#xD;
                  males who are sexually active with a female partner of childbearing potential&#xD;
                  must use a male condom plus spermicide from screening through 180 days after&#xD;
                  receipt of the final dose of durvalumab + tremelimumab combination therapy or 90&#xD;
                  days after receipt of the final dose of durvalumab monotherapy. Not engaging in&#xD;
                  sexual activity is an acceptable practice; however, occasional abstinence, the&#xD;
                  rhythm method, and the withdrawal method are not acceptable methods of&#xD;
                  contraception. Male patients should refrain from sperm donation throughout this&#xD;
                  period.&#xD;
&#xD;
         21. Any condition that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of study treatment or interpretation of patient safety or study results&#xD;
&#xD;
         22. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive&#xD;
             of but not limited to surgery, radiation and/or corticosteroids.&#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>carla van Herpen, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Amsterdam UMC</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMC Groningen</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leiden UMC</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>January 9, 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>January 6, 2022</last_update_submitted>
  <last_update_submitted_qc>January 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>durvalumab</keyword>
  <keyword>PD-L1 imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_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/NCT03829007
org study id: PINCH
nct id: NCT03829007
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Non-invasive imaging of tumor PD-L1 expression with 89Zr-labeled durvalumab PET/CT predicts
      response to durvalumab.
The programmed death 1 (PD1)/ programmed death ligand 1 (PD-L1) pathway plays an important
      role in regulating the T-cell anti tumor response. Blocking this interaction with the anti
      PD-L1 monoclonal antibody durvalumab has proven to be effective resulting in durable disease
      control rates. Currently, PD-L1 expression as determined by immune histochemistry (IH) is the
      best available biomarker for treatment response, but standardized scoring criteria are
      lacking and the risk for sampling errors exists. Molecular imaging using 89Zr-labeled
      antibodies may overcome these limitations, enabling the visualization of PD-L1 expression in
      primary and metastatic tumor lesions and providing information on the in vivo accessibility
      of the PD-L1 target following intravenous administration. Besides, a baseline FDG-PET scan
      will be performed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Tumor uptake of 89Zr-durvalumab
time frame: 1 year
description: standardized uptake values (SUV) of 89Zr-durvalumab uptake in tumor lesions will be measured.
measure: To assess the potential of PD-L1 PET imaging to predict disease control rate of patients with recurrent or advanced head and neck cancer treated with durvalumab q4w 1500mg iv
time frame: 1-2 year
description: PD-L1 PET imaging performed with the optimal dose as assessed in part 1 of the study
measure: Correlation between tumor uptake of 89Zr-durvalumab and PD-L1 expression as determined immunohistochemically
time frame: 1-2 years
description: PD-L1 expression performed by Ventana SP263
arm group label: PD-L1 imaging
arm group type: Experimental
description: 89Zr-durvalumab iv injection followed by a PET/CT scan at day 5 after injection.
intervention type: Diagnostic Test
intervention name: PD-L1 imaging
description: 89Zr-durvalumab injection followed by a PET/CT scan 5 days after injection
arm group label: PD-L1 imaging
other name: 89Zr-durvalumab PET/CT
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab treatment is initiated after the PET/CT scan in a fixed dose of 1500 mg iv q4w
arm group label: PD-L1 imaging
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: carla van Herpen, Prof
role: Principal Investigator
affiliation: Radboud University Medical Center
facility: 
facility: 
facility: 
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
mesh term: Durvalumab
mesh term: Antibodies, Monoclonal