<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/NCT02983578</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0108</org_study_id>
    <secondary_id>NCI-2018-01296</secondary_id>
    <secondary_id>2016-0108</secondary_id>
    <nct_id>NCT02983578</nct_id>
  </id_info>
  <brief_title>Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer</brief_title>
  <official_title>Phase II Clinical Trial Evaluating Intravenous AZD9150 (Antisense STAT3) With MEDI4736 (Anti-PD-L1) in Patients With Advanced Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well danvatirsen and durvalumab work in treating patients&#xD;
      with pancreatic cancer, non-small cell lung cancer and mismatch repair deficient colorectal&#xD;
      cancer that has spread to other places in the body and does not respond to treatment.&#xD;
      Danvatirsen may be used to block the production of proteins needed for tumor cell growth.&#xD;
      Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune&#xD;
      system attack the cancer, and may interfere with the ability of tumor cells to grow and&#xD;
      spread. Giving danvatirsen and durvalumab may work better at treating pancreatic cancer,&#xD;
      non-small cell lung cancer and mismatch repair deficient colorectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Evaluate disease control rate (DCR) at 4 months. II. Evaluate tumor-based biomarkers in&#xD;
      paired pre and post treatment biopsies (10 in each arm, 30 total) that may correlate with&#xD;
      treatment or prospectively identify patients likely to respond to treatment with danvatirsen&#xD;
      (AZD9150) in combination with durvalumab (MEDI4736) (may include PD-L1 expression,&#xD;
      phosphorylated or total STAT3 expression, tumor genetics, characterization of immune&#xD;
      infiltrates, or other stratification markers).&#xD;
&#xD;
      III. Explore the relationship between PD-L1 protein levels in the membrane of circulating&#xD;
      tumor cells obtained by peripheral blood draws prior to, during, and after treatment with&#xD;
      clinical endpoints including treatment efficacy and toxicity.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Evaluate the frequency of dose limiting toxicities. II. Evaluate frequency of objective&#xD;
      response (as defined as partial response [PR] or complete response [CR] according to Response&#xD;
      Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria).&#xD;
&#xD;
      III. Evaluate duration of response (DOR) measured from the time measurement criteria are&#xD;
      first met for CR or PR, whichever is first recorded, until the first date that recurrent or&#xD;
      progressive disease (PD) is objectively documented.&#xD;
&#xD;
      IV. Evaluate best overall response (including CR, PR, stable disease [SD], and PD, according&#xD;
      to RECIST version 1.1 criteria).&#xD;
&#xD;
      V. Evaluate progression free survival (PFS) from allocation to the first documentation of PD&#xD;
      as determined by the investigator or death from any cause, whichever occurs first.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. Explore the relationship between radiologic metrics (radiomics) prior to, during, and&#xD;
      after treatment with clinical endpoints including treatment efficacy and toxicity.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive danvatirsen intravenously (IV) over 1 hour on days 7, 5 and 3 prior to cycle&#xD;
      1, then on days 1, 8, 15 and 22. Patients also receive durvalumab IV over 1 hour on day 1.&#xD;
      Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days, 1-3 months, then&#xD;
      every 2 months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 2, 2017</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 30, 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>Incidence of adverse events (AEs), serious AEs</measure>
    <time_frame>Up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Physiological parameters (Laboratory evaluations)</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Blood samples for routine coagulation assessments will be obtained at screening and once during week 4 of cycle 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of treatment-emergent AEs (TEAEs), SAEs and death(s)</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Will be graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PD-L1 expression</measure>
    <time_frame>Up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phosphorylated or total STAT3 expression levels</measure>
    <time_frame>Up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Characterization of immune infiltrates</measure>
    <time_frame>Up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantification and characterization of CD8 staining pattern</measure>
    <time_frame>Up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PD-L1 protein levels in the membrane of circulating tumor cells</measure>
    <time_frame>Baseline up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Physiological parameters</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Vital signs will required at screening before dosing on Day -7 of the Lead-in; before dosing on Days 1, 8, 15, and 22 of each cycle; and at the EOT visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical Examinations</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>A complete physical examination is required at screening, before dosing on Day 7 of the Lead in, before dosing on Day 1 of each cycle, and at the EOT visit. A targeted physical examination as directed by disease, signs and symptoms is required before dosing on Day 15 of each cycle.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control</measure>
    <time_frame>At 4 months</time_frame>
    <description>Will be defined as a compete response (CR), partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Will be defined as a CR or PR according to RECIST version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response according to RECIST version 1.1 criteria</measure>
    <time_frame>From the time measurement criteria are first met for CR or PR, assessed up to 4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response (including CR, PR, SD, and progressive disease [PD], according to RECIST version 1.1 criteria)</measure>
    <time_frame>Up to 4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>From allocation assessed up to 4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From start of treatment assessed up to 4 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Radiomic measurements</measure>
    <time_frame>Baseline up to 4 years</time_frame>
    <description>These are IRECIST measurements</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Advanced Colorectal Carcinoma</condition>
  <condition>Advanced Lung Non-Small Cell Carcinoma</condition>
  <condition>Lung Non-Small Cell Carcinoma</condition>
  <condition>Mismatch Repair Deficiency</condition>
  <condition>Refractory Colorectal Carcinoma</condition>
  <condition>Refractory Lung Carcinoma</condition>
  <condition>Refractory Pancreatic Carcinoma</condition>
  <condition>Stage II Pancreatic Cancer AJCC v8</condition>
  <condition>Stage III Colorectal Cancer AJCC v8</condition>
  <condition>Stage III Lung Cancer AJCC v8</condition>
  <condition>Stage III Pancreatic Cancer AJCC v8</condition>
  <condition>Stage IIIA Colorectal Cancer AJCC v8</condition>
  <condition>Stage IIIA Lung Cancer AJCC v8</condition>
  <condition>Stage IIIB Colorectal Cancer AJCC v8</condition>
  <condition>Stage IIIB Lung Cancer AJCC v8</condition>
  <condition>Stage IIIC Colorectal Cancer AJCC v8</condition>
  <condition>Stage IIIC Lung Cancer AJCC v8</condition>
  <condition>Stage IV Colorectal Cancer AJCC v8</condition>
  <condition>Stage IV Lung Cancer AJCC v8</condition>
  <condition>Stage IV Pancreatic Cancer AJCC v8</condition>
  <condition>Stage IVA Colorectal Cancer AJCC v8</condition>
  <condition>Stage IVA Lung Cancer AJCC v8</condition>
  <condition>Stage IVB Colorectal Cancer AJCC v8</condition>
  <condition>Stage IVB Lung Cancer AJCC v8</condition>
  <condition>Stage IVC Colorectal Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Treatment (danvatirsen, durvalumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive danvatirsen IV over 1 hour on days 7, 5 and 3 prior to cycle 1, then on days 1, 8, 15 and 22. Patients also receive durvalumab IV over 1 hour on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Danvatirsen</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (danvatirsen, durvalumab)</arm_group_label>
    <other_name>AZD9150</other_name>
    <other_name>ISIS 481464</other_name>
    <other_name>ISIS-STAT3rx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (danvatirsen, durvalumab)</arm_group_label>
    <other_name>Imfinzi</other_name>
    <other_name>Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer</other_name>
    <other_name>MEDI-4736</other_name>
    <other_name>MEDI4736</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient/legal representative must be able to read and understand the informed&#xD;
             consent form (ICF) and must have been willing to give written informed consent and any&#xD;
             locally required authorization (e.g., Health Insurance Portability and Accountability&#xD;
             Act in the United States of America [USA]; European Union Data Privacy Directive in&#xD;
             the European Union [EU]) before any study-specific procedures, including screening&#xD;
             evaluations, sampling, and analyses&#xD;
&#xD;
          -  Has a histological confirmation of pancreatic cancer, mismatch deficient colorectal&#xD;
             cancer, or non-small cell lung cancer (NSCLC) that is refractory to standard therapy&#xD;
             or for which no standard of care regimen currently exists&#xD;
&#xD;
          -  Has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) score of 0 or&#xD;
             1&#xD;
&#xD;
          -  Has measurable disease, defined as at least 1 lesion that can be accurately measured&#xD;
             in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm&#xD;
             by computerized tomography (CT) scan, except lymph nodes which must have minimum short&#xD;
             axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases).&#xD;
             Indicator lesions must not have been previously treated with surgery, radiation&#xD;
             therapy, or radiofrequency ablation unless there is documented progression after&#xD;
             therapy&#xD;
&#xD;
          -  Transfusions intended to elevate any parameters below solely for the intent of meeting&#xD;
             study eligibility are not permitted&#xD;
&#xD;
          -  Leukocytes &gt;= 3000 mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1500 mcL&#xD;
&#xD;
          -  Platelets &gt; = 100 000 mcL&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Total bilirubin =&lt; 3 x ULN in patients with documented Gilbert's syndrome&#xD;
             (unconjugated hyperbilirubinemia) or in the presence of liver metastases&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 2.5 x ULN if no&#xD;
             demonstrable liver metastases or =&lt; 5 x ULN in the presence of liver metastases&#xD;
&#xD;
          -  Creatinine within normal limits OR, for patients with levels above institutional&#xD;
             normal: creatinine clearance measured by 24-hour urine collection &gt;= 60 mL/min, OR&#xD;
             calculated corrected creatinine clearance &gt;= 60 mL/min/1.73 m^2 using the&#xD;
             Cockcroft-Gault formula (Cockcroft and Gault 1976) corrected for the body surface area&#xD;
&#xD;
          -  Women of childbearing potential and men who are sexually active with a female partner&#xD;
             of childbearing potential must be surgically sterilized, practicing abstinence, or&#xD;
             agree to use 2 birth control methods before study entry, for the duration of study&#xD;
             participation, and for 20 weeks after the final dose of study drug; cessation of birth&#xD;
             control after this point should be discussed with a responsible physician. Women of&#xD;
             childbearing potential are defined as those who are not surgically sterile (i.e.,&#xD;
             bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or&#xD;
             postmenopausal (defined as 12 months with no menses without an alternative medical&#xD;
             cause). Two methods of contraception which are considered accurate per protocol must&#xD;
             be combined. Periodic abstinence, the rhythm method, and the withdrawal method are not&#xD;
             acceptable methods of birth control&#xD;
&#xD;
          -  Women of childbearing potential also may not be breast feeding and must have a&#xD;
             negative serum or urine pregnancy test within 72 hours before the start of study&#xD;
             treatment&#xD;
&#xD;
          -  The patient/legal representative must be willing to provide written consent for&#xD;
             collection of formalin fixed paraffin-embedded blocks or slides from archival&#xD;
             diagnostic histology samples, where available&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a spinal cord compression unless asymptomatic, radiographically stable over the&#xD;
             last 4 weeks, and not requiring steroids for at least 4 weeks before the start of&#xD;
             study treatment&#xD;
&#xD;
          -  Presently has a second malignancy other than squamous cell carcinoma of the head and&#xD;
             neck (SCCHN), or history of treatment for invasive cancer other than SCCHN in the past&#xD;
             3 years. Exceptions are:&#xD;
&#xD;
               -  Previously treated in-situ carcinoma (i.e., noninvasive)&#xD;
&#xD;
               -  Cervical carcinoma stage 1B or less&#xD;
&#xD;
               -  Noninvasive basal cell and squamous cell skin carcinoma&#xD;
&#xD;
               -  Radically treated prostate cancer (prostatectomy or radiotherapy) with normal&#xD;
                  prostate-specific antigen, and not requiring ongoing antiandrogen hormonal&#xD;
                  therapy&#xD;
&#xD;
          -  Patients must have completed previous cancer-related treatments before enrollment. Any&#xD;
             concurrent chemotherapy, radiotherapy, immunotherapy, or biologic, or hormonal therapy&#xD;
             for cancer excludes the patient (concurrent use of hormones for noncancer-related&#xD;
             conditions [e.g., insulin for diabetes or hormone replacement therapy] is acceptable).&#xD;
             The following intervals between end of the prior treatment and first dose of study&#xD;
             drug must be observed:&#xD;
&#xD;
               -  Port-a-cath placement: no waiting required&#xD;
&#xD;
               -  Minor surgical procedures: &gt;= 7 postoperative days&#xD;
&#xD;
               -  Major surgery: &gt;= 4 weeks&#xD;
&#xD;
               -  Radiotherapy: &gt;= 4 weeks&#xD;
&#xD;
               -  Chemotherapy: &gt;= 4 weeks&#xD;
&#xD;
               -  Immunotherapy or investigational anticancer therapy with agents other than&#xD;
                  monoclonal antibodies (mAbs): &gt;= 4 weeks&#xD;
&#xD;
               -  Immunotherapy or investigational anticancer therapy with mAbs: &gt;= 6 weeks&#xD;
&#xD;
               -  Immunosuppressive medication: &gt;= 4 weeks with the exceptions of intranasal or&#xD;
                  inhaled corticosteroids or systemic corticosteroids at physiologic doses not to&#xD;
                  exceed 10 mg/day of prednisone or equivalent&#xD;
&#xD;
          -  Is still experiencing toxicity related to prior treatment and assessed as Common&#xD;
             Terminology Criteria for Adverse Events (CTCAE) grade &gt; 1. Exceptions are alopecia&#xD;
             and/or anorexia. The eligibility of patients who are still experiencing irreversible&#xD;
             toxicity that is not reasonably expected to be exacerbated by the study drugs in this&#xD;
             study (e.g., hearing loss) must be reviewed and approved by both the principal&#xD;
             investigator and medical monitor&#xD;
&#xD;
          -  Has experienced immune-related adverse events (AEs) (irAEs) while receiving prior&#xD;
             immunotherapy (including anti-CTLA4 treatment) and assessed as CTCAE grade &gt;= 3&#xD;
&#xD;
          -  Has active or prior documented autoimmune disease within the past 2 years with the&#xD;
             exceptions of vitiligo, Grave's disease, and/or psoriasis not requiring systemic&#xD;
             treatment&#xD;
&#xD;
          -  Has active or prior documented inflammatory bowel disease (e.g., Crohn's disease,&#xD;
             ulcerative colitis)&#xD;
&#xD;
          -  Has a history of primary immunodeficiency&#xD;
&#xD;
          -  Has undergone an organ transplant that requires use of immunosuppressive treatment&#xD;
&#xD;
          -  Has a history of interstitial lung disease or pneumonitis from any cause&#xD;
&#xD;
          -  Has a history of allergic reactions attributed to the study treatments (AZD9150 or&#xD;
             MEDI4736), their compounds, or agents of similar chemical or biologic composition&#xD;
             (e.g., antibody therapeutics)&#xD;
&#xD;
          -  Suffers from a comorbidity that in the opinion of the investigator renders the patient&#xD;
             unsuitable for participation in the study. Such comorbidity may include, but is not&#xD;
             limited to, uncontrolled intercurrent illness such as active infection, severe active&#xD;
             peptic ulcer disease or gastritis, myocardial infarction within 6 months before entry,&#xD;
             congestive heart failure, symptomatic congestive heart failure, active cardiomyopathy,&#xD;
             unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or&#xD;
             psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements&#xD;
&#xD;
          -  As judged by the investigator, has any evidence of severe or uncontrolled systemic&#xD;
             diseases such as active bleeding diatheses, is positive for human immunodeficiency&#xD;
             virus (HIV), or has active hepatitis B virus (HBV) and/or hepatitis C virus (HCV)&#xD;
&#xD;
          -  Has a known history of tuberculosis&#xD;
&#xD;
          -  Has a condition that, in the opinion of the investigator, would interfere with the&#xD;
             evaluation of the study drugs or the interpretation of patient safety or study results&#xD;
&#xD;
          -  Has received a live attenuated vaccine within 28 days before the first dose of study&#xD;
             drug&#xD;
&#xD;
          -  Judgment by the investigator that the patient should not participate in the study if&#xD;
             the patient is unlikely to comply with study procedures, restrictions, and&#xD;
             requirements&#xD;
&#xD;
          -  Patients with clinically active brain metastases (known or suspected) are excluded&#xD;
             unless the brain metastases have been previously treated and are considered stable.&#xD;
             Stable brain metastases are defined as no change on CT scan or magnetic resonance&#xD;
             imaging (MRI) scan for a minimum of 2 months AND no change in steroid dose for a&#xD;
             minimum of 4 weeks, unless change due to intercurrent infection or other acute event&#xD;
&#xD;
          -  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;
      </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>David S Hong</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>March 13, 2023</last_update_submitted>
  <last_update_submitted_qc>March 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 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>Colorectal Neoplasms</mesh_term>
    <mesh_term>Pancreatic 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>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Immunoglobulin G</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/NCT02983578
org study id: 2016-0108
secondary id: NCI-2018-01296
secondary id: 2016-0108
nct id: NCT02983578
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well danvatirsen and durvalumab work in treating patients
      with pancreatic cancer, non-small cell lung cancer and mismatch repair deficient colorectal
      cancer that has spread to other places in the body and does not respond to treatment.
      Danvatirsen may be used to block the production of proteins needed for tumor cell growth.
      Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune
      system attack the cancer, and may interfere with the ability of tumor cells to grow and
      spread. Giving danvatirsen and durvalumab may work better at treating pancreatic cancer,
      non-small cell lung cancer and mismatch repair deficient colorectal cancer.
PRIMARY OBJECTIVES:

      I. Evaluate disease control rate (DCR) at 4 months. II. Evaluate tumor-based biomarkers in
      paired pre and post treatment biopsies (10 in each arm, 30 total) that may correlate with
      treatment or prospectively identify patients likely to respond to treatment with danvatirsen
      (AZD9150) in combination with durvalumab (MEDI4736) (may include PD-L1 expression,
      phosphorylated or total STAT3 expression, tumor genetics, characterization of immune
      infiltrates, or other stratification markers).

      III. Explore the relationship between PD-L1 protein levels in the membrane of circulating
      tumor cells obtained by peripheral blood draws prior to, during, and after treatment with
      clinical endpoints including treatment efficacy and toxicity.

      SECONDARY OBJECTIVES:

      I. Evaluate the frequency of dose limiting toxicities. II. Evaluate frequency of objective
      response (as defined as partial response [PR] or complete response [CR] according to Response
      Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria).

      III. Evaluate duration of response (DOR) measured from the time measurement criteria are
      first met for CR or PR, whichever is first recorded, until the first date that recurrent or
      progressive disease (PD) is objectively documented.

      IV. Evaluate best overall response (including CR, PR, stable disease [SD], and PD, according
      to RECIST version 1.1 criteria).

      V. Evaluate progression free survival (PFS) from allocation to the first documentation of PD
      as determined by the investigator or death from any cause, whichever occurs first.

      EXPLORATORY OBJECTIVES:

      I. Explore the relationship between radiologic metrics (radiomics) prior to, during, and
      after treatment with clinical endpoints including treatment efficacy and toxicity.

      OUTLINE:

      Patients receive danvatirsen intravenously (IV) over 1 hour on days 7, 5 and 3 prior to cycle
      1, then on days 1, 8, 15 and 22. Patients also receive durvalumab IV over 1 hour on day 1.
      Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, 1-3 months, then
      every 2 months thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events (AEs), serious AEs
time frame: Up to 4 years
measure: Physiological parameters (Laboratory evaluations)
time frame: Up to 4 years
description: Blood samples for routine coagulation assessments will be obtained at screening and once during week 4 of cycle 1.
measure: Incidence of treatment-emergent AEs (TEAEs), SAEs and death(s)
time frame: Up to 4 years
description: Will be graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03.
measure: PD-L1 expression
time frame: Up to 4 years
measure: Phosphorylated or total STAT3 expression levels
time frame: Up to 4 years
measure: Characterization of immune infiltrates
time frame: Up to 4 years
measure: Quantification and characterization of CD8 staining pattern
time frame: Up to 4 years
measure: PD-L1 protein levels in the membrane of circulating tumor cells
time frame: Baseline up to 4 years
measure: Physiological parameters
time frame: Up to 4 years
description: Vital signs will required at screening before dosing on Day -7 of the Lead-in; before dosing on Days 1, 8, 15, and 22 of each cycle; and at the EOT visit.
measure: Physical Examinations
time frame: Up to 4 years
description: A complete physical examination is required at screening, before dosing on Day 7 of the Lead in, before dosing on Day 1 of each cycle, and at the EOT visit. A targeted physical examination as directed by disease, signs and symptoms is required before dosing on Day 15 of each cycle.
measure: Disease control
time frame: At 4 months
description: Will be defined as a compete response (CR), partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
measure: Objective response
time frame: Up to 4 years
description: Will be defined as a CR or PR according to RECIST version 1.1.
measure: Duration of response according to RECIST version 1.1 criteria
time frame: From the time measurement criteria are first met for CR or PR, assessed up to 4 years
measure: Best overall response (including CR, PR, SD, and progressive disease [PD], according to RECIST version 1.1 criteria)
time frame: Up to 4 years
measure: Progression free survival
time frame: From allocation assessed up to 4 years
measure: Overall survival
time frame: From start of treatment assessed up to 4 years
measure: Radiomic measurements
time frame: Baseline up to 4 years
description: These are IRECIST measurements
arm group label: Treatment (danvatirsen, durvalumab)
arm group type: Experimental
description: Patients receive danvatirsen IV over 1 hour on days 7, 5 and 3 prior to cycle 1, then on days 1, 8, 15 and 22. Patients also receive durvalumab IV over 1 hour on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Danvatirsen
description: Given IV
arm group label: Treatment (danvatirsen, durvalumab)
other name: AZD9150
other name: ISIS 481464
other name: ISIS-STAT3rx
intervention type: Biological
intervention name: Durvalumab
description: Given IV
arm group label: Treatment (danvatirsen, durvalumab)
other name: Imfinzi
other name: Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
other name: MEDI-4736
other name: MEDI4736
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David S Hong
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Colorectal Neoplasms
mesh term: Pancreatic Neoplasms
mesh term: Durvalumab
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoglobulin G