<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/NCT03798626</url>
  </required_header>
  <id_info>
    <org_study_id>CVPM087A2101</org_study_id>
    <secondary_id>2018-003952-19</secondary_id>
    <nct_id>NCT03798626</nct_id>
  </id_info>
  <brief_title>Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers</brief_title>
  <official_title>Phase Ib Study of Gevokizumab in Combination With Standard of Care Anti-cancer Therapies in Patients With Metastatic Colorectal Cancer, Gastroesophageal Cancer and Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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 study will determine the pharmacodynamically-active dose of gevokizumab and the&#xD;
      tolerable dose of gevokizumab in combination with the standard of care anti-cancer therapy in&#xD;
      patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic&#xD;
      renal cell carcinoma, and the preliminary efficacy of gevokizumab in combination with the SOC&#xD;
      anti-cancer therapy in subjects with mCRC and mGEC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 22, 2019</start_date>
  <completion_date type="Anticipated">October 28, 2024</completion_date>
  <primary_completion_date type="Actual">March 1, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy</measure>
    <time_frame>Baseline, Day 15</time_frame>
    <description>Log scale change of hs-CRP at Day 15 from baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D]</measure>
    <time_frame>First 4 weeks of combination treatment</time_frame>
    <description>DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B]</measure>
    <time_frame>First 6 weeks of combination treatment</time_frame>
    <description>DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level]</measure>
    <time_frame>At 15 months</time_frame>
    <description>PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level]</measure>
    <time_frame>At 9 months</time_frame>
    <description>PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level]</measure>
    <time_frame>At 6 months</time_frame>
    <description>PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR) per investigator assessment using RECIST v1.1</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>ORR is defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) per investigator assessment using RECIST v1.1</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) per investigator assessment using RECIST v1.1</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>OS is defined as the time from date of first dose of study treatment to date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level]</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of gevokizumab, as monotherapy and in the combination regimens</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>To characterize the pharmacokinetics of gevokizumab therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of bevacizumab</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>To characterize the pharmacokinetics of bevacizumab therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of ramucirumab</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>To characterize the pharmacokinetics of ramucirumab therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of irinotecan</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>To characterize the pharmacokinetics of irinotecan therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of paclitaxel</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>To characterize the pharmacokinetics of paclitaxel therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of cabozantinib</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>To characterize the pharmacokinetics of cabozantinib therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with anti-drug antibodies for gevokizumab in the combination regimens</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Incidence of immunogenicity for gevokizumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with anti-drug antibodies for bevacizumab in the combination regimens</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Incidence of immunogenicity for bevacizumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with anti-drug antibodies for ramucirumab in the combination regimens</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Incidence of immunogenicity for ramucirumab</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">167</enrollment>
  <condition>Colorectal Cancer</condition>
  <condition>Gastroesophageal Cancer</condition>
  <condition>Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Cohort A: 1st line colorectal cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B: 2nd line colorectal cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C: 2nd line gastroesophageal cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D: 2nd or 3rd line renal cell carcinoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gevokizumab</intervention_name>
    <description>60 mg/mL concentration; administered intravenously (IV)</description>
    <arm_group_label>Cohort A: 1st line colorectal cancer</arm_group_label>
    <arm_group_label>Cohort B: 2nd line colorectal cancer</arm_group_label>
    <arm_group_label>Cohort C: 2nd line gastroesophageal cancer</arm_group_label>
    <arm_group_label>Cohort D: 2nd or 3rd line renal cell carcinoma</arm_group_label>
    <other_name>VPM087</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>25 mg/mL concentration; administered IV</description>
    <arm_group_label>Cohort A: 1st line colorectal cancer</arm_group_label>
    <arm_group_label>Cohort B: 2nd line colorectal cancer</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Modified FOLFOX6</intervention_name>
    <description>Oxaliplatin [5 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV]</description>
    <arm_group_label>Cohort A: 1st line colorectal cancer</arm_group_label>
    <other_name>oxaliplatin, leucovorin, 5-fluorouracil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRI</intervention_name>
    <description>Irinotecan [20 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV]</description>
    <arm_group_label>Cohort B: 2nd line colorectal cancer</arm_group_label>
    <other_name>irinotecan, leucovorin, 5-fluorouracil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ramucirumab</intervention_name>
    <description>10 mg/mL concentration; administered IV</description>
    <arm_group_label>Cohort C: 2nd line gastroesophageal cancer</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>6 mg/mL concentration; administered IV</description>
    <arm_group_label>Cohort C: 2nd line gastroesophageal cancer</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabozantinib</intervention_name>
    <description>60 mg tablet; administered orally</description>
    <arm_group_label>Cohort D: 2nd or 3rd line renal cell carcinoma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic disease not amenable to potentially curative surgery and with available&#xD;
             archival tumor tissue or fresh tumor tissue biopsy.&#xD;
&#xD;
          -  Presence of at least 1 measurable lesion assessed by CT and/or MRI according to RECIST&#xD;
             1.1.&#xD;
&#xD;
        For Cohort A:&#xD;
&#xD;
        - First line metastatic colorectal cancer.&#xD;
&#xD;
        For Cohort B:&#xD;
&#xD;
        - Second line metastatic colorectal cancer that has progressed on prior chemotherapy&#xD;
        administered for metastatic disease and which must include a fluoropyrimidine and&#xD;
        oxaliplatin.&#xD;
&#xD;
        For Cohort C:&#xD;
&#xD;
        - Second line metastatic gastroesophageal cancer that has progressed on prior line of&#xD;
        chemotherapy administered for metastatic disease, and which must include a platinum agent&#xD;
        and fluoropyrimidine doublet.&#xD;
&#xD;
        For Cohort D:&#xD;
&#xD;
        - Second or third line metastatic renal cell carcinoma with a clear-cell component and has&#xD;
        received one or two lines of treatment for metastatic disease that included an&#xD;
        anti-angiogenic agent for at least 4 weeks with radiologic progression on that treatment.&#xD;
&#xD;
        For subjects starting from Part 1a in Cohorts A and B:&#xD;
&#xD;
          -  Serum hs-CRP at screening ≥ 10 mg/L.&#xD;
&#xD;
          -  Not requiring immediate initiation of anti-cancer therapy per investigator's best&#xD;
             judgement.&#xD;
&#xD;
        For subjects starting from Part 2 in Cohort C:&#xD;
&#xD;
        - Serum hs-CRP at screening ≥ 10 mg/L.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For All Cohorts:&#xD;
&#xD;
          -  Currently receiving any of the prohibited medications or has contraindications as&#xD;
             outlined in the protocol.&#xD;
&#xD;
          -  Symptomatic brain metastases or brain metastases that require directed therapy (such&#xD;
             as focal radiotherapy or surgery).&#xD;
&#xD;
          -  Suspected or proven immunocompromised state, or infections (as defined in the&#xD;
             protocol).&#xD;
&#xD;
          -  Conditions that have a high risk of clinically significant bleeding after&#xD;
             administration of anti-VEGF agents.&#xD;
&#xD;
          -  Clinically significant, uncontrolled or recent (within last 6 months) cardiovascular&#xD;
             disease.&#xD;
&#xD;
        For Cohort D:&#xD;
&#xD;
          -  Concomitant medications, herbal supplements, and/or fruits and their juices that are&#xD;
             known as strong inhibitors or inducers of CYP3A4/5, and medications that have a narrow&#xD;
             therapeutic window and are predominantly metabolized through CYP3A4/5.&#xD;
&#xD;
          -  Impairment of GI function or GI disease that may significantly alter the absorption of&#xD;
             cabozantinib.&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Los Angeles UCLA Oncology Clinic</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School Siteman Cancer Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute Drug Ship - 4</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edegem</city>
        <state>Antwerpen</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Santiago</city>
        <zip>8330074</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brno</city>
        <state>Czech Republic</state>
        <zip>656 53</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Frankfurt</city>
        <zip>60488</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ramat Gan</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rozzano</city>
        <state>MI</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>464 8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>277 8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Osaka-city</city>
        <state>Osaka</state>
        <zip>541-8567</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sunto Gun</city>
        <state>Shizuoka</state>
        <zip>411 8777</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bunkyo-ku</city>
        <state>Tokyo</state>
        <zip>113-8603</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sevilla</city>
        <state>Andalucia</state>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hospitalet de LLobregat</city>
        <state>Catalunya</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valencia</city>
        <state>Comunidad Valenciana</state>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tainan</city>
        <zip>70403</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Argentina</country>
    <country>Austria</country>
    <country>Hong Kong</country>
  </removed_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>colorectal cancer</keyword>
  <keyword>gastroesophageal cancer</keyword>
  <keyword>renal cell carcinoma</keyword>
  <keyword>gevokizumab</keyword>
  <keyword>bevacizumab</keyword>
  <keyword>modified FOLFOX6</keyword>
  <keyword>FOLFIRI</keyword>
  <keyword>ramucirumab</keyword>
  <keyword>paclitaxel</keyword>
  <keyword>cabozantinib</keyword>
  <keyword>CRC</keyword>
  <keyword>GEC</keyword>
  <keyword>RCC</keyword>
  <keyword>VPM087</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Ramucirumab</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03798626
org study id: CVPM087A2101
secondary id: 2018-003952-19
nct id: NCT03798626
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will determine the pharmacodynamically-active dose of gevokizumab and the
      tolerable dose of gevokizumab in combination with the standard of care anti-cancer therapy in
      patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic
      renal cell carcinoma, and the preliminary efficacy of gevokizumab in combination with the SOC
      anti-cancer therapy in subjects with mCRC and mGEC.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy
time frame: Baseline, Day 15
description: Log scale change of hs-CRP at Day 15 from baseline
measure: Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D]
time frame: First 4 weeks of combination treatment
description: DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
measure: Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B]
time frame: First 6 weeks of combination treatment
description: DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
measure: Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level]
time frame: At 15 months
description: PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
measure: Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level]
time frame: At 9 months
description: PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
measure: Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level]
time frame: At 6 months
description: PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
measure: Overall response rate (ORR) per investigator assessment using RECIST v1.1
time frame: Up to 5 years
description: ORR is defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), according to RECIST 1.1
measure: Duration of response (DOR) per investigator assessment using RECIST v1.1
time frame: Up to 5 years
description: Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria
measure: Disease Control Rate (DCR) per investigator assessment using RECIST v1.1
time frame: Up to 5 years
description: DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.
measure: Overall survival (OS)
time frame: Up to 5 years
description: OS is defined as the time from date of first dose of study treatment to date of death due to any cause.
measure: PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level]
time frame: Up to 5 years
description: PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
measure: PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B)
time frame: Up to 5 years
description: PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
measure: Serum concentration of gevokizumab, as monotherapy and in the combination regimens
time frame: Up to 5 years
description: To characterize the pharmacokinetics of gevokizumab therapy
measure: Serum concentration of bevacizumab
time frame: Up to 5 years
description: To characterize the pharmacokinetics of bevacizumab therapy
measure: Serum concentration of ramucirumab
time frame: Up to 5 years
description: To characterize the pharmacokinetics of ramucirumab therapy
measure: Serum concentration of irinotecan
time frame: Up to 3 months
description: To characterize the pharmacokinetics of irinotecan therapy
measure: Serum concentration of paclitaxel
time frame: Up to 3 months
description: To characterize the pharmacokinetics of paclitaxel therapy
measure: Serum concentration of cabozantinib
time frame: Up to 3 months
description: To characterize the pharmacokinetics of cabozantinib therapy
measure: Number of patients with anti-drug antibodies for gevokizumab in the combination regimens
time frame: Up to 5 years
description: Incidence of immunogenicity for gevokizumab
measure: Number of patients with anti-drug antibodies for bevacizumab in the combination regimens
time frame: Up to 5 years
description: Incidence of immunogenicity for bevacizumab
measure: Number of patients with anti-drug antibodies for ramucirumab in the combination regimens
time frame: Up to 5 years
description: Incidence of immunogenicity for ramucirumab
arm group label: Cohort A: 1st line colorectal cancer
arm group type: Experimental
description: Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab
arm group label: Cohort B: 2nd line colorectal cancer
arm group type: Experimental
description: Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab
arm group label: Cohort C: 2nd line gastroesophageal cancer
arm group type: Experimental
description: Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab
arm group label: Cohort D: 2nd or 3rd line renal cell carcinoma
arm group type: Experimental
description: Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib
intervention type: Drug
intervention name: Gevokizumab
description: 60 mg/mL concentration; administered intravenously (IV)
arm group label: Cohort A: 1st line colorectal cancer
arm group label: Cohort B: 2nd line colorectal cancer
arm group label: Cohort C: 2nd line gastroesophageal cancer
arm group label: Cohort D: 2nd or 3rd line renal cell carcinoma
other name: VPM087
intervention type: Drug
intervention name: Bevacizumab
description: 25 mg/mL concentration; administered IV
arm group label: Cohort A: 1st line colorectal cancer
arm group label: Cohort B: 2nd line colorectal cancer
intervention type: Drug
intervention name: Modified FOLFOX6
description: Oxaliplatin [5 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV]
arm group label: Cohort A: 1st line colorectal cancer
other name: oxaliplatin, leucovorin, 5-fluorouracil
intervention type: Drug
intervention name: FOLFIRI
description: Irinotecan [20 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV]
arm group label: Cohort B: 2nd line colorectal cancer
other name: irinotecan, leucovorin, 5-fluorouracil
intervention type: Drug
intervention name: Ramucirumab
description: 10 mg/mL concentration; administered IV
arm group label: Cohort C: 2nd line gastroesophageal cancer
intervention type: Drug
intervention name: Paclitaxel
description: 6 mg/mL concentration; administered IV
arm group label: Cohort C: 2nd line gastroesophageal cancer
intervention type: Drug
intervention name: Cabozantinib
description: 60 mg tablet; administered orally
arm group label: Cohort D: 2nd or 3rd line renal cell carcinoma
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Australia
country: Belgium
country: Canada
country: Chile
country: Czechia
country: Germany
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Singapore
country: Spain
country: Taiwan
country: United Kingdom
country: United States
country: Argentina
country: Austria
country: Hong Kong
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Colorectal Neoplasms
mesh term: Carcinoma, Renal Cell
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Bevacizumab
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Irinotecan
mesh term: Ramucirumab
mesh term: Levoleucovorin
sharing ipd: No