<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/NCT03804866</url>
  </required_header>
  <id_info>
    <org_study_id>NGR018-IPR/26</org_study_id>
    <secondary_id>2012-005745-20</secondary_id>
    <nct_id>NCT03804866</nct_id>
  </id_info>
  <brief_title>NGR-hTNF in Combination With an Anthracycline in Platinum-resistant Ovarian Cancer (NGR018)</brief_title>
  <official_title>NGR018: Randomized Phase II Study of NGR-hTNF Plus an Anthracycline Versus an Anthracycline Alone in Platinum-resistant Ovarian Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AGC Biologics S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AGC Biologics S.p.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this extension protocol is to evaluate the early safety of a new&#xD;
      schedule of NGR-hTNF given weekly, instead of every 3 or 4 weeks, in a cohort of 12 patients&#xD;
      randomized to the experimental arm A, as compared to a reference cohort of 12 patients&#xD;
      randomized to an anthracycline alone&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this extension protocol IPR/26 of completed IPR/24 study, considering the relatively short&#xD;
      half-life of approximately 1 hour and the favourable toxicity profile of NGR-hTNF,&#xD;
      characterized by transient constitutional symptoms occurring during the first day of&#xD;
      administration, an additional cohort of 24 patients will be randomized and the 12 patients&#xD;
      enrolled in arm A will receive the same dose of NGR-hTNF 0.8 mcg/m2 given as 60 minutes&#xD;
      infusion every week. the weekly schedule of NGR-hTNF 0.8 mcg/m2 has previously been tested in&#xD;
      several studies&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2013</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety according to NCI-CTCAE criteria (version 4.03)</measure>
    <time_frame>from the start of treatment until 28 days after last treatment</time_frame>
    <description>To evaluate safety profile related to NGR-hTNF</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months</time_frame>
    <description>Defined as the time from the date of randomization until disease progression, or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>from randomization date, every 6-8 weeks based on type of chemotherapy during treatment and every 12 weeks during follow-up until date of death, from any cause, assessed up through study completion, approximately 12 months</time_frame>
    <description>defined as the time from the date of randomization until death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Rate (RR)</measure>
    <time_frame>from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months</time_frame>
    <description>defined as the percentage of patients who have a best-response rating of complete or partial response, according to standard RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months</time_frame>
    <description>defined as the percentage of patients who have a best-response rating of complete response, partial response, or stable disease, according to standard RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Disease Control</measure>
    <time_frame>from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months</time_frame>
    <description>measured from the date of randomization until disease progression, or death due to any cause</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A: NGR-hTNF+ anthracycline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: anthracycline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pegylated Liposomal Doxorubicin or Doxorubicin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NGR-hTNF</intervention_name>
    <description>NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs</description>
    <arm_group_label>Arm A: NGR-hTNF+ anthracycline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegylated liposomal doxorubicin</intervention_name>
    <description>50 mg/m² iv every 4 weeks until confirmed evidence of disease progression</description>
    <arm_group_label>Arm A: NGR-hTNF+ anthracycline</arm_group_label>
    <arm_group_label>Arm B: anthracycline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>60 mg/m² iv every 3 weeks for a maximum of 8 cycles</description>
    <arm_group_label>Arm A: NGR-hTNF+ anthracycline</arm_group_label>
    <arm_group_label>Arm B: anthracycline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Histologically-proven ovarian cancer, fallopian tube and primary peritoneal cancer in&#xD;
             advanced or metastatic stage&#xD;
&#xD;
          -  Patients previously treated with a maximum of two platinum-based regimen plus&#xD;
             paclitaxel and with documented progressive disease on treatment (refractory patient&#xD;
             population) or within 6 months from last chemotherapy cycle (resistant patient&#xD;
             population)&#xD;
&#xD;
          -  ECOG Performance status 0 - 2&#xD;
&#xD;
          -  Life expectancy of 12 weeks or more&#xD;
&#xD;
          -  Normal cardiac function and absence of uncontrolled hypertension&#xD;
&#xD;
          -  Adequate baseline bone marrow, hepatic and renal function defined as follows:&#xD;
&#xD;
               1. Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               2. Bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               3. AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in&#xD;
                  presence of liver metastasis&#xD;
&#xD;
               4. Serum creatinine &lt; 1.5 x ULN&#xD;
&#xD;
          -  At least one (not previously irradiated) target lesion or non-measurable disease only,&#xD;
             according to RECIST criteria&#xD;
&#xD;
          -  Patients may have had prior therapy providing the following conditions are met:&#xD;
&#xD;
               1. Surgery and radiation therapy: wash-out period of 14 days&#xD;
&#xD;
               2. Systemic anti-tumor therapy: wash-out period of 21 days&#xD;
&#xD;
          -  Patients must give written informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must not receive any other investigational agents while on study&#xD;
&#xD;
          -  More than two previous chemotherapy lines and previous treatment with anthracycline&#xD;
&#xD;
          -  Patients with myocardial infarction within the last six months, unstable angina, New&#xD;
             York Heart Association (NYHA) grade II or greater congestive heart failure, or serious&#xD;
             cardiac arrhythmia requiring medication&#xD;
&#xD;
          -  Prolonged QTc interval (congenital or acquired) &gt; 450 ms&#xD;
&#xD;
          -  History or evidence upon physical examination of CNS disease unless adequately treated&#xD;
&#xD;
          -  Patients with active or uncontrolled systemic disease/infections or with serious&#xD;
             illness or medical conditions, which is incompatible with the protocol&#xD;
&#xD;
          -  Known hypersensitivity/allergic reaction or contraindications to human albumin&#xD;
             preparations or to any of the excipients&#xD;
&#xD;
          -  Any psychological, familial, sociological or geographical condition potentially&#xD;
             hampering compliance with the study protocol&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antonio Lambiase, MD</last_name>
    <role>Study Director</role>
    <affiliation>AGC Biologics S.p.A.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia</name>
      <address>
        <city>Milan</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori IRCCS Fondazione &quot;Giovanni Pascale&quot;</name>
      <address>
        <city>Naples</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>October 3, 2018</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>January 14, 2019</last_update_submitted>
  <last_update_submitted_qc>January 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NGR-hTNF</keyword>
  <keyword>Pegylated liposomal doxorubicin</keyword>
  <keyword>Doxorubicin</keyword>
  <keyword>Platinum-resistant</keyword>
  <keyword>Progression or recurrence Ovarian Cancer</keyword>
  <keyword>Ovarian Cancer</keyword>
  <keyword>Advanced or metastatic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</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/NCT03804866
org study id: NGR018-IPR/26
secondary id: 2012-005745-20
nct id: NCT03804866
lead sponsor: 
has dmc: No
The primary objective of this extension protocol is to evaluate the early safety of a new
      schedule of NGR-hTNF given weekly, instead of every 3 or 4 weeks, in a cohort of 12 patients
      randomized to the experimental arm A, as compared to a reference cohort of 12 patients
      randomized to an anthracycline alone
In this extension protocol IPR/26 of completed IPR/24 study, considering the relatively short
      half-life of approximately 1 hour and the favourable toxicity profile of NGR-hTNF,
      characterized by transient constitutional symptoms occurring during the first day of
      administration, an additional cohort of 24 patients will be randomized and the 12 patients
      enrolled in arm A will receive the same dose of NGR-hTNF 0.8 mcg/m2 given as 60 minutes
      infusion every week. the weekly schedule of NGR-hTNF 0.8 mcg/m2 has previously been tested in
      several studies
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety according to NCI-CTCAE criteria (version 4.03)
time frame: from the start of treatment until 28 days after last treatment
description: To evaluate safety profile related to NGR-hTNF
measure: Progression-Free Survival (PFS)
time frame: from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months
description: Defined as the time from the date of randomization until disease progression, or death
measure: Overall survival (OS)
time frame: from randomization date, every 6-8 weeks based on type of chemotherapy during treatment and every 12 weeks during follow-up until date of death, from any cause, assessed up through study completion, approximately 12 months
description: defined as the time from the date of randomization until death due to any cause
measure: Response Rate (RR)
time frame: from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months
description: defined as the percentage of patients who have a best-response rating of complete or partial response, according to standard RECIST criteria
measure: Disease Control Rate (DCR)
time frame: from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months
description: defined as the percentage of patients who have a best-response rating of complete response, partial response, or stable disease, according to standard RECIST criteria
measure: Duration of Disease Control
time frame: from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months
description: measured from the date of randomization until disease progression, or death due to any cause
arm group label: Arm A: NGR-hTNF+ anthracycline
arm group type: Experimental
description: NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin
arm group label: Arm B: anthracycline
arm group type: Active Comparator
description: Pegylated Liposomal Doxorubicin or Doxorubicin
intervention type: Drug
intervention name: NGR-hTNF
description: NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
arm group label: Arm A: NGR-hTNF+ anthracycline
intervention type: Drug
intervention name: Pegylated liposomal doxorubicin
description: 50 mg/m² iv every 4 weeks until confirmed evidence of disease progression
arm group label: Arm A: NGR-hTNF+ anthracycline
arm group label: Arm B: anthracycline
intervention type: Drug
intervention name: Doxorubicin
description: 60 mg/m² iv every 3 weeks for a maximum of 8 cycles
arm group label: Arm A: NGR-hTNF+ anthracycline
arm group label: Arm B: anthracycline
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antonio Lambiase, MD
role: Study Director
affiliation: AGC Biologics S.p.A.
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin