<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/NCT03007030</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0514</org_study_id>
    <secondary_id>NCI-2017-00069</secondary_id>
    <secondary_id>2016-0514</secondary_id>
    <nct_id>NCT03007030</nct_id>
  </id_info>
  <brief_title>Brentuximab Vedotin in Treating Patients With CD30+ Malignant Mesothelioma That Cannot Be Removed by Surgery</brief_title>
  <official_title>Phase II Trial of Adcetris (Brentuximab Vedotin) in CD30+ Malignant Mesothelioma</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>
  </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 brentuximab vedotin works in treating patients with CD30&#xD;
      positive (+) malignant mesothelioma that cannot be removed by surgery. Monoclonal antibodies,&#xD;
      such as brentuximab vedotin, may interfere with the ability of tumor cells to grow and&#xD;
      spread.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess 4-month disease control rate (DCR) in pre-treated patients with unresectable&#xD;
      malignant pleural mesothelioma (MPM) treated with brentuximab vedotin.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the response rate, progression-free and overall survival, and safety/toxicity&#xD;
      of brentuximab vedotin in CD30+ malignant mesothelioma.&#xD;
&#xD;
      II. To prospectively evaluate the incidence of CD30+ expression in malignant mesothelioma&#xD;
      during the screening process.&#xD;
&#xD;
      III. To determine whether CD30+ expression levels in tumor tissue correlate to response to&#xD;
      brentuximab vedotin.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To collect archival or new tissue and blood for correlative studies. II. Next generation&#xD;
      sequencing (NGS) will be conducted on adequate tumor tissue specimens.&#xD;
&#xD;
      III. Exploratory analysis: Bank peripheral blood at baseline for subsequent cytokine or&#xD;
      reverse phase protein array (RPPA).&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Courses&#xD;
      repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days, 3 months, 6 months&#xD;
      and then every 6 months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 5, 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>Disease control rate (DCR) defined as proportion of patients who had complete response, partial response or stable disease by Response Evaluation Criteria in Solid Tumors version 4.1</measure>
    <time_frame>At 4 months</time_frame>
    <description>A DCR of 50% or higher is considered as clinically significant. If the trial is not stopped early and all 50 patients are accrued, point estimate along with 95% credible interval will be provided. Logistic regression model will be utilized to assess the effect of patient prognostic factors on the response status if sufficient number of patients with stable disease or better response to the treatment are observed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor characteristics</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Patients' demographic and tumor characteristics will be analyzed, with categorical variables summarized in frequency tables while continuous variables summarized using mean (plus or minus standard deviation) and median (range). The student t-test/Wilcoxon test and analysis of variance (ANOVA)/Kruskal-Wallis test will be used to compare continuous variables between different patient groups. The chi-square test or the Fisher's exact test will be applied to assess the association between two categorical variables.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. Cox proportional hazard regression will be employed for multi-covariate analysis on time-to-event outcomes when appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. Cox proportional hazard regression will be employed for multi-covariate analysis on time-to-event outcomes when appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD30+ expression levels</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The student t-test/Wilcoxon test and ANOVA/Kruskal-Wallis test will be used to compare CD30+ expression levels by response status.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cytokines in peripheral blood</measure>
    <time_frame>At time of disease progression, assessed up to 5 years</time_frame>
    <description>Appropriate statistical approaches will be applied to the exploratory analysis of the cytokines.</description>
  </other_outcome>
  <other_outcome>
    <measure>Reverse phase protein array (RPPA) in peripheral blood</measure>
    <time_frame>At time of disease progression, assessed up to 5 years</time_frame>
    <description>Appropriate statistical approaches will be applied to the exploratory analysis of RPPA.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>CD30-Positive Neoplastic Cells Present</condition>
  <condition>Malignant Mesothelioma</condition>
  <arm_group>
    <arm_group_label>Treatment (brentuximab vedotin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (brentuximab vedotin)</arm_group_label>
    <other_name>ADC SGN-35</other_name>
    <other_name>Adcetris</other_name>
    <other_name>Anti-CD30 Antibody-Drug Conjugate SGN-35</other_name>
    <other_name>Anti-CD30 Monoclonal Antibody-MMAE SGN-35</other_name>
    <other_name>Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35</other_name>
    <other_name>cAC10-vcMMAE</other_name>
    <other_name>SGN-35</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (brentuximab vedotin)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Voluntary written informed consent before performance of any study-related procedure&#xD;
             not part of normal medical care, with the understanding that consent may be withdrawn&#xD;
             by the subject at any time without prejudice to future medical care&#xD;
&#xD;
          -  Female subject is either: a. post-menopausal for at least one year before the&#xD;
             screening visit; or b. surgically sterilized; or c. willing to use an acceptable&#xD;
             method of birth control (i.e., a hormonal contraceptive, intra-uterine device,&#xD;
             diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of&#xD;
             the study and at least 6 months after the last dose of brentuximab vedotin&#xD;
&#xD;
          -  Male subject, even if surgically sterilized (i.e., status postvasectomy), agrees to&#xD;
             use an acceptable barrier method for contraception (condom with a spermicidal agent),&#xD;
             or completely abstain from heterosexual intercourse during the entire study treatment&#xD;
             period through 6 months after the last dose of brentuximab vedotin&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt; 1500/mm^3&#xD;
&#xD;
          -  Platelets &gt; 100,000/mm^3&#xD;
&#xD;
          -  Hemoglobin (Hgb) &gt; 8.5 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and&#xD;
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) &lt; 3 x&#xD;
             ULN; AST and/or ALT may be up to 5 X ULN if with known liver metastases (mets)&#xD;
&#xD;
          -  Calculated creatinine clearance must be &gt;= 30 mL/minute&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Pathologic diagnosis of malignant mesothelioma (any primary site is acceptable, any&#xD;
             histology is acceptable)&#xD;
&#xD;
          -  Have unresectable malignant mesothelioma (any histology)&#xD;
&#xD;
          -  Positive CD30+ immunohistochemical expression&#xD;
&#xD;
          -  Any line of prior therapy - patients may be chemo-naive or chemo-refractory (any line)&#xD;
&#xD;
          -  Patients must have measurable disease by modified Response Evaluation Criteria in&#xD;
             Solid Tumors (RECIST) or RECIST; examinations for assessment of measurable disease&#xD;
             must have been completed within 28 days prior to registration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Radiation therapy to more than 25% of the bone marrow; whole pelvic radiation is&#xD;
             considered to be over 25%&#xD;
&#xD;
          -  Prior allogeneic bone marrow or organ transplantation&#xD;
&#xD;
          -  Female subject who is pregnant or breast-feeding; confirmation that the subject is not&#xD;
             pregnant must be established by a negative serum beta-human chorionic gonadotropin&#xD;
             (B-hCG) pregnancy test result obtained during screening; pregnancy testing is not&#xD;
             required for post-menopausal or surgically sterilized women&#xD;
&#xD;
          -  Patient has received other investigational drugs with 14 days before enrollment&#xD;
&#xD;
          -  Serious medical or psychiatric illness likely to interfere with participation in this&#xD;
             clinical study&#xD;
&#xD;
          -  No prior history of malignancy within 2 years, unless cured of a skin cancer or a&#xD;
             stage I-III solid tumor; no prior hematologic malignancy within 3 years&#xD;
&#xD;
          -  Known hypersensitivity to brentuximab vedotin components&#xD;
&#xD;
          -  Persons who are incarcerated at time of enrollment (e.g., prisoners) or likely to&#xD;
             become incarcerated during the 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>Anne S Tsao</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anne S. Tsao</last_name>
    <phone>713-792-6363</phone>
    <email>astsao@mdanderson.org</email>
  </overall_contact>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Anne S. Tsao</last_name>
      <phone>713-792-6363</phone>
    </contact>
    <investigator>
      <last_name>Anne S. Tsao</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>M D Anderson Cancer Center</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 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>Mesothelioma</mesh_term>
    <mesh_term>Mesothelioma, Malignant</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Brentuximab Vedotin</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Immunoconjugates</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/NCT03007030
org study id: 2016-0514
secondary id: NCI-2017-00069
secondary id: 2016-0514
nct id: NCT03007030
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well brentuximab vedotin works in treating patients with CD30
      positive (+) malignant mesothelioma that cannot be removed by surgery. Monoclonal antibodies,
      such as brentuximab vedotin, may interfere with the ability of tumor cells to grow and
      spread.
PRIMARY OBJECTIVES:

      I. To assess 4-month disease control rate (DCR) in pre-treated patients with unresectable
      malignant pleural mesothelioma (MPM) treated with brentuximab vedotin.

      SECONDARY OBJECTIVES:

      I. To evaluate the response rate, progression-free and overall survival, and safety/toxicity
      of brentuximab vedotin in CD30+ malignant mesothelioma.

      II. To prospectively evaluate the incidence of CD30+ expression in malignant mesothelioma
      during the screening process.

      III. To determine whether CD30+ expression levels in tumor tissue correlate to response to
      brentuximab vedotin.

      EXPLORATORY OBJECTIVES:

      I. To collect archival or new tissue and blood for correlative studies. II. Next generation
      sequencing (NGS) will be conducted on adequate tumor tissue specimens.

      III. Exploratory analysis: Bank peripheral blood at baseline for subsequent cytokine or
      reverse phase protein array (RPPA).

      OUTLINE:

      Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Courses
      repeat every 21 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, 3 months, 6 months
      and then every 6 months thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease control rate (DCR) defined as proportion of patients who had complete response, partial response or stable disease by Response Evaluation Criteria in Solid Tumors version 4.1
time frame: At 4 months
description: A DCR of 50% or higher is considered as clinically significant. If the trial is not stopped early and all 50 patients are accrued, point estimate along with 95% credible interval will be provided. Logistic regression model will be utilized to assess the effect of patient prognostic factors on the response status if sufficient number of patients with stable disease or better response to the treatment are observed.
measure: Tumor characteristics
time frame: Up to 5 years
description: Patients' demographic and tumor characteristics will be analyzed, with categorical variables summarized in frequency tables while continuous variables summarized using mean (plus or minus standard deviation) and median (range). The student t-test/Wilcoxon test and analysis of variance (ANOVA)/Kruskal-Wallis test will be used to compare continuous variables between different patient groups. The chi-square test or the Fisher's exact test will be applied to assess the association between two categorical variables.
measure: Time to progression
time frame: Up to 5 years
description: The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. Cox proportional hazard regression will be employed for multi-covariate analysis on time-to-event outcomes when appropriate.
measure: Overall survival
time frame: Up to 5 years
description: The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. Cox proportional hazard regression will be employed for multi-covariate analysis on time-to-event outcomes when appropriate.
measure: CD30+ expression levels
time frame: Up to 5 years
description: The student t-test/Wilcoxon test and ANOVA/Kruskal-Wallis test will be used to compare CD30+ expression levels by response status.
measure: Cytokines in peripheral blood
time frame: At time of disease progression, assessed up to 5 years
description: Appropriate statistical approaches will be applied to the exploratory analysis of the cytokines.
measure: Reverse phase protein array (RPPA) in peripheral blood
time frame: At time of disease progression, assessed up to 5 years
description: Appropriate statistical approaches will be applied to the exploratory analysis of RPPA.
arm group label: Treatment (brentuximab vedotin)
arm group type: Experimental
description: Patients receive brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Brentuximab Vedotin
description: Given IV
arm group label: Treatment (brentuximab vedotin)
other name: ADC SGN-35
other name: Adcetris
other name: Anti-CD30 Antibody-Drug Conjugate SGN-35
other name: Anti-CD30 Monoclonal Antibody-MMAE SGN-35
other name: Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35
other name: cAC10-vcMMAE
other name: SGN-35
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (brentuximab vedotin)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anne S Tsao
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
last name: Anne S. Tsao
phone: 713-792-6363
email: astsao@mdanderson.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: M D Anderson Cancer Center
responsible party type: Sponsor
mesh term: Mesothelioma
mesh term: Mesothelioma, Malignant
mesh term: Lung Neoplasms
mesh term: Antineoplastic Agents, Immunological
mesh term: Brentuximab Vedotin
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoconjugates