<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/NCT03750786</url>
  </required_header>
  <id_info>
    <org_study_id>ISO-CC-007</org_study_id>
    <nct_id>NCT03750786</nct_id>
  </id_info>
  <brief_title>A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer</brief_title>
  <acronym>AGENT</acronym>
  <official_title>A Randomized, Multicenter, Parallel-group, Phase III Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Isofol Medical AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Isofol Medical AB</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, randomized, parallel-group, Phase III study in at least 440 patients&#xD;
      with advanced colorectal cancer to compare the efficacy of treatment with arfolitixorin&#xD;
      versus Leucovorin in combination with 5-fluorouracil, oxaliplatin, and bevacizumab according&#xD;
      to modified FOLFOX-6 until PD according to RECIST 1.1 criteria.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 18, 2018</start_date>
  <completion_date type="Anticipated">January 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2022</primary_completion_date>
  <phase>Phase 3</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Until disease progression, an average of ten months</time_frame>
    <description>Best ORR, defined as the best response recorded from the start of the study treatment until the end of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Until disease progression, an average of ten months</time_frame>
    <description>PFS, defined as the time from randomization to first occurrence of tumor progression based on CT-scans/MRIs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Until disease progression, an average of ten months</time_frame>
    <description>The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">490</enrollment>
  <condition>Colo-rectal Cancer</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ARFOX (Arfolitixorin and 5-FU and Oxaliplatin) and Bevacizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>mFOLFOX-6 (Leucovorin and 5-FU and Oxaliplatin) and Bevacizumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Arfolitixorin</intervention_name>
    <description>Arfolitixorin and 5-FU and Oxaliplatin and Bevacizumab</description>
    <arm_group_label>Group A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>Leucovorin and 5-FU and Oxaliplatin and Bevacizumab</description>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Colorectal adenocarcinoma verified by biopsy.&#xD;
&#xD;
          2. Availability of biopsy material, from the primary tumor or metastasis, allowing for&#xD;
             analysis of tumor gene expression.&#xD;
&#xD;
          3. Non-resectable metastatic CRC planned for first line therapy with 5-FU, oxaliplatin,&#xD;
             and bevacizumab.&#xD;
&#xD;
          4. Evaluable disease with at least one measurable lesion of metastatic disease (≥10 mm in&#xD;
             longest diameter on axial image on CT-scan or alternatively MRI with &lt;5 mm&#xD;
             reconstruction interval) obtained within 28 days of randomization.&#xD;
&#xD;
          5. Life expectancy of more than 4 months.&#xD;
&#xD;
          6. ECOG performance status 0 or 1.&#xD;
&#xD;
          7. Hemoglobin (Hb) &gt; 100 g/L, Absolute neutrophil count (ANC) &gt; 1.5x109/L. Thrombocytes &gt;&#xD;
             100x109/L.&#xD;
&#xD;
          8. Creatinine clearance &gt; 50 mL/min, Total bilirubin &lt; 1.5 x ULN, AST and ALT &lt; 3 x ULN&#xD;
             (and &lt; 5 x ULN in case of liver metastases).&#xD;
&#xD;
          9. Male or female ≥18 years of age.&#xD;
&#xD;
         10. Female patients of childbearing potential must have a negative urine pregnancy test&#xD;
             and use adequate contraceptive measures . Male patients must use adequate&#xD;
             contraceptive measures .&#xD;
&#xD;
         11. Voluntarily signed 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 patient at any time without prejudice to future medical care.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Malignant tumors other than colorectal adenocarcinomas (current or within the previous&#xD;
             five years), with the exception for curatively treated non-melanoma skin cancer or in&#xD;
             situ carcinoma of the cervix.&#xD;
&#xD;
          2. Less than 6 months between randomization and completion of the last anti-cancer&#xD;
             treatment (chemotherapy/radiotherapy/immunotherapy/surgery, etc.). (NB: Rectal cancer&#xD;
             treatment shorter than 8 weeks of chemo/radiation therapy is allowed.)&#xD;
&#xD;
          3. Confirmation of progressive disease within 6 months after completion of prior&#xD;
             anti-cancer treatment.&#xD;
&#xD;
          4. Indication for any metastatic Colo-rectal Cancer (mCRC) surgery or anti-cancer&#xD;
             treatment other than study treatment.&#xD;
&#xD;
          5. Prior treatment with arfolitixorin.&#xD;
&#xD;
          6. Indication for treatment with a 5-FU analogue, or 5-FU for a condition other than&#xD;
             mCRC.&#xD;
&#xD;
          7. Known Dihydropyrimidine Dehydrogenase Deficiency (DPD) deficiency.&#xD;
&#xD;
          8. Known or suspected central nervous system (CNS) metastases.&#xD;
&#xD;
          9. Unresolved bowel obstruction, uncontrolled Crohn's disease, or ulcerative colitis.&#xD;
&#xD;
         10. History of cardiac disease with a New York Heart Association Class II or greater,&#xD;
             congestive heart failure, myocardial infarction, or unstable angina at any time during&#xD;
             the 6 months prior to randomization, or serious arrhythmias requiring medication for&#xD;
             treatment.&#xD;
&#xD;
         11. Current CTCAE ≥ grade 3 diarrhea.&#xD;
&#xD;
         12. Current chronic infection or uncontrolled serious illness causing immunodeficiency.&#xD;
&#xD;
         13. Known or suspected hypersensitivity or intolerance to arfolitixorin, LV, 5-FU,&#xD;
             oxaliplatin, or bevacizumab.&#xD;
&#xD;
         14. Breastfeeding patients.&#xD;
&#xD;
         15. Patient who received investigational drugs in other clinical trials within 28 days, or&#xD;
             5 half-lives of the investigational drug, prior to randomization.&#xD;
&#xD;
         16. Patient with serious medical or psychiatric illness likely to interfere with&#xD;
             participation in this clinical study.&#xD;
&#xD;
         17. Ongoing drug or alcohol abuse, as deemed by the Investigator.&#xD;
&#xD;
         18. Any condition that, in the opinion of the Investigator, could compromise the patient's&#xD;
             safety or adherence to the study protocol.&#xD;
&#xD;
         19. Involvement, or related to people involved in the planning or conduct of the study&#xD;
             (applies to both Isofol Medical AB (publ) staff and staff at the study site)&#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>Josep Tabernero, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vall d'Hebron Institute of Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>840-24 - Banner Gateway Medical Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-01 - University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>91001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-15 - HOAG Memorial Hospital</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-13 - UCH-MHS d/b/a Memorial Health System</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-34 - Banner MD Anderson Cancer Center</name>
      <address>
        <city>Greeley</city>
        <state>Colorado</state>
        <zip>80631</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-32 - University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-08 - Pinellas Hematology Oncology</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33709</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-30 - Joliet Oncology-Hematology Associates</name>
      <address>
        <city>Joliet</city>
        <state>Illinois</state>
        <zip>60435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-06 - Cancer Center of Kansas</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-29 - Ashland-Bellefonte Cancer Center</name>
      <address>
        <city>Ashland</city>
        <state>Kentucky</state>
        <zip>41101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-19 - University of Louisville Research Foundation Inc. (ULRF)</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202-1798</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-14 - University of Michigan Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-04 - St. Vincent Frontier Cancer Center</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-12 - Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-22 - University of Oklahoma Stephenson Cancer Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-10 - Oregon Health and Science University-Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-27 - Charleston Hematology Oncology Associates</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>840-02 - The University of Texas Health Science Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>036-10 - Border Medical Oncology Research Unit</name>
      <address>
        <city>Albury</city>
        <state>New South Wales</state>
        <zip>2640</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>036-02 - Chris O'Brien Lifehouse</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>036-03 - Westmead Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>036-09 - Southern Medical Day Care Center</name>
      <address>
        <city>Wollongong</city>
        <state>New South Wales</state>
        <zip>2500</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>036-04 - Peninsula Health - Frankston Hospital</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>036-01 - Western Health - Sunshine Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3021</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>036-07 - Northern Health - Epping Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3076</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>036-05 - Monash Health</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>040-02 - Klinikum Klagenfurt am Wörthersee</name>
      <address>
        <city>Klagenfurt</city>
        <zip>9020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>040-06 - Ordensklinikum Linz GmbH - Barmherzige Schwestern</name>
      <address>
        <city>Linz</city>
        <zip>4010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>040-03 - Landeskrankenhaus</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>040-04 - Landesklinikum Wiener Neustadt</name>
      <address>
        <city>Wiener Neustadt</city>
        <zip>2700</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>040-01 - Allgemeines Krankenhaus der Stadt Wien</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>040-05 - Wilhelminenspital</name>
      <address>
        <city>Wien</city>
        <zip>1160</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-03 - William Osler Health System - Brampton Civi Hospital</name>
      <address>
        <city>Brampton</city>
        <state>Ontario</state>
        <zip>L6R 3J7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-10 - Thunder Bay Regional Health Research Institute</name>
      <address>
        <city>Thunder Bay</city>
        <state>Ontario</state>
        <zip>P7B 6V4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-07 - Sunnybrook Research Institute</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-04 - CISSS de l'Outaouais - Hôpital de Gatineau</name>
      <address>
        <city>Gatineau</city>
        <state>Quebec</state>
        <zip>J8V 2L4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-11 - CISSS de Chaudière-Appalaches</name>
      <address>
        <city>Lévis</city>
        <state>Quebec</state>
        <zip>G6V 3Z1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-01 - Montreal University Health Center</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-02 - Hôpital de la Cité-de-la-Santé</name>
      <address>
        <city>Laval</city>
        <zip>H7M 3L9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-08 - Hôpital Maisonneuve Rosemont</name>
      <address>
        <city>Montréal</city>
        <zip>H1T 2M4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-06 - Jewish General Hospital</name>
      <address>
        <city>Montréal</city>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>124-05 - Ottawa Hospital Research Institute</name>
      <address>
        <city>Ottawa</city>
        <zip>KIH8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-07 - Hôpital Henri Mondor</name>
      <address>
        <city>Créteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-06 - Centre Georges Francois Leclerc</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-01 - Institute Hospitalier Franco-Britannique</name>
      <address>
        <city>Levallois-Perret</city>
        <zip>92300</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-09 - Hopital Privé Jean Mermoz</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-08 - Hôpital Européen</name>
      <address>
        <city>Marseille</city>
        <zip>13003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-03 - Hôpital Paris Saint Joseph</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-02 - Hôpital Saint-Antoine</name>
      <address>
        <city>Paris</city>
        <zip>75571</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-04 - Polyclinique Francheville</name>
      <address>
        <city>Périgueux</city>
        <zip>24000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>250-05 - Clinique Sainte Anne</name>
      <address>
        <city>Strasbourg</city>
        <zip>67000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-12 - Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-02 - Universitätsklinikum Carl Gustav Carus</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-03 - Krankenhaus Nordwest GmbH</name>
      <address>
        <city>Frankfurt am Main</city>
        <zip>60488</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-10 - Universitärers Cancer Center Hamburg (UCCH)</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-11 - Klinikum Kassel GmbH</name>
      <address>
        <city>Kassel</city>
        <zip>34125</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-04 - MVZ Mitte - Onkologische Schwerpunktpraxis</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-13 - Universitäres Krebszentrum Leipzig (UCCL)</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-07 - Philipps-Universität Marburg</name>
      <address>
        <city>Marburg</city>
        <zip>35032</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-08 - Carl von Basedow Klinikum Saalekrei GmbH</name>
      <address>
        <city>Merseburg</city>
        <zip>06217</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-01 - Klinikum der Universität München - Campus Grosshadern</name>
      <address>
        <city>München</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-09 - Klinikum Nürnberg Nord</name>
      <address>
        <city>Nürnberg</city>
        <zip>90419</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>276-05 - Kliniken Nordoberpfalz AG</name>
      <address>
        <city>Weiden</city>
        <zip>92637</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>300-04 - 251 Airforce Hospital</name>
      <address>
        <city>Athens</city>
        <zip>11525</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>300-01 - Aretaieo Hospital</name>
      <address>
        <city>Athens</city>
        <zip>11528</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>300-02 - University General Hospital Attikon</name>
      <address>
        <city>Athens</city>
        <zip>15562</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>300-03 - Metropolitan General Hospital</name>
      <address>
        <city>Athens</city>
        <zip>15562</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>300-05 - Metropolitan General SA</name>
      <address>
        <city>Athen</city>
        <zip>15562</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>300-06 - University General Hospital of Larissa</name>
      <address>
        <city>Larissa</city>
        <zip>41110</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-10 - Aichi Cancer Center</name>
      <address>
        <city>Aichi</city>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-01 - National Cancer Center Hospital East</name>
      <address>
        <city>Chiba</city>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-09 - National Hospital Organization Shikoku Cancer Center</name>
      <address>
        <city>Ehime</city>
        <zip>791-0280</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-07 - Gifu University Hospital</name>
      <address>
        <city>Gifu City</city>
        <zip>501-1194</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-12 - Saitama Medical University International Medical Center</name>
      <address>
        <city>Hidaka City</city>
        <zip>350-1298</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-05 - University of Tsukuba Hospital</name>
      <address>
        <city>Ibaraki</city>
        <zip>305-8576</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-15 - Kagawa University Hospital</name>
      <address>
        <city>Kagawa</city>
        <zip>761-0793</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-08 - St.Marianna University School of Medicine Hospital</name>
      <address>
        <city>Kanagawa</city>
        <zip>216-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-11 - National Hospital Organization Osaka National Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>540-0006</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-13 - Osaka General Medical Center</name>
      <address>
        <city>Osaka</city>
        <zip>558-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-14 - Kansai Medical University Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>573-1191</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-04 - Saitama Cancer Center</name>
      <address>
        <city>Saitama</city>
        <zip>362-0806</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-03 - Hokkaido University Hospital</name>
      <address>
        <city>Sapporo Hokkaido</city>
        <zip>060-8648</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-02 - Shizuoka Cancer Center</name>
      <address>
        <city>Shizuoka</city>
        <zip>411-8777</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>392-06 - National Cancer Center Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>724-03 - Instituto Oncologico Baselga - Hospital Quiron</name>
      <address>
        <city>Barcelona</city>
        <zip>08023</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>724-07 - Hospital del la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>724-01 - Vall d'Hebron Institute of Oncology</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>724-06 - Hospital Universitario Reina Sofia</name>
      <address>
        <city>Córdoba</city>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>724-04 - Hospital Unviersitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>724-09 - Hospital Universitario HM Sanchinarro</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>724-02 - Hospital Regional Universitario Carlos Haya</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>724-05 - Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>752-02 - Södersjukhuset</name>
      <address>
        <city>Stockholm</city>
        <zip>118 83</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>752-01 - Akademiska Sjukhuset</name>
      <address>
        <city>Uppsala</city>
        <zip>751 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Japan</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>March 29, 2022</last_update_submitted>
  <last_update_submitted_qc>March 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</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>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>August 18, 2023</submitted>
    <submission_canceled>August 30, 2023</submission_canceled>
    <submitted>September 1, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03750786
org study id: ISO-CC-007
nct id: NCT03750786
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a multicenter, randomized, parallel-group, Phase III study in at least 440 patients
      with advanced colorectal cancer to compare the efficacy of treatment with arfolitixorin
      versus Leucovorin in combination with 5-fluorouracil, oxaliplatin, and bevacizumab according
      to modified FOLFOX-6 until PD according to RECIST 1.1 criteria.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Overall response rate
time frame: Until disease progression, an average of ten months
description: Best ORR, defined as the best response recorded from the start of the study treatment until the end of treatment.
measure: Progression free survival
time frame: Until disease progression, an average of ten months
description: PFS, defined as the time from randomization to first occurrence of tumor progression based on CT-scans/MRIs.
measure: Duration of response
time frame: Until disease progression, an average of ten months
description: The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented.
arm group label: Group A
arm group type: Experimental
description: ARFOX (Arfolitixorin and 5-FU and Oxaliplatin) and Bevacizumab
arm group label: Group B
arm group type: Active Comparator
description: mFOLFOX-6 (Leucovorin and 5-FU and Oxaliplatin) and Bevacizumab
intervention type: Drug
intervention name: Arfolitixorin
description: Arfolitixorin and 5-FU and Oxaliplatin and Bevacizumab
arm group label: Group A
intervention type: Drug
intervention name: Leucovorin
description: Leucovorin and 5-FU and Oxaliplatin and Bevacizumab
arm group label: Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Josep Tabernero, Prof.
role: Principal Investigator
affiliation: Vall d'Hebron Institute of Oncology
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country: Australia
country: Austria
country: Canada
country: France
country: Germany
country: Greece
country: Japan
country: Spain
country: Sweden
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Leucovorin
submitted: August 18, 2023
submission canceled: August 30, 2023
submitted: September 1, 2023