<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/NCT02244632</url>
  </required_header>
  <id_info>
    <org_study_id>ISO-CC-005</org_study_id>
    <secondary_id>2014-001862-84</secondary_id>
    <nct_id>NCT02244632</nct_id>
  </id_info>
  <brief_title>Modufolin (Arfolitixorin) in Combination With 5-Fluorouracil Alone or Together With Oxaliplatin or Irinotecan in Colorectal Cancer</brief_title>
  <official_title>An Open-label, Multiple-site, Phase I/II Dose Cohort Trial of [6R] 5,10-Methylene Tetrahydrofolate (Modufolin®) in Combination With a Fixed Dose of 5-Fluorouracil (5-FU) Alone or Together With a Fixed Dose of Oxaliplatin or Irinotecan in Patients With Stage IV 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>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose is to characterise the tolerability of Modufolin (arfolitixorin) in combination&#xD;
      with 5-FU alone, in combination with 5-FU and Oxaliplatin, in combination with 5-FU and&#xD;
      Irinotecan and in combination with 5-FU, Oxaliplatin and Bevacizumab.&#xD;
&#xD;
      Another purpose is to investigate 4 doses of Modufolin to identify the best dose for further&#xD;
      assessment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will investigate the tolerability of Modufolin at four (4) different dose levels&#xD;
      (30 to 240 mg/m2) in therapy combinations with the chemotherapeutic agents 5-FU, Oxaliplatin&#xD;
      +/- bevcizumab, and Irinotecan.&#xD;
&#xD;
      When the selected phase 2 dose is determined, 40 additional patients, will be included in the&#xD;
      study in order to acquire more data on the safety and tolerability of Modufolin at this dose&#xD;
      level. Twenty (20) of these additional patients will be treated in with Oxaliplatin, 20 with&#xD;
      Irinotecan.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">January 30, 2020</completion_date>
  <primary_completion_date type="Actual">January 30, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Frequency and severity of dose limiting toxicity (DLT) or other Adverse Events (AE)</measure>
    <time_frame>The patients will be followed during 4 cycles of treatment (8 weeks).</time_frame>
    <description>Primary safety variables will consist of monitoring and recording of DLTs and any significant AE that have led to adjustments in the therapy administration.</description>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">105</enrollment>
  <condition>Colorectal Neoplasm</condition>
  <arm_group>
    <arm_group_label>Modufolin / Nordic FLV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Modufolin in combination with 5-Fluorouracil only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Modufolin / Nordic FLOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to Nordic FLOX regime</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Modufolin / Nordic FLIRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Modufolin in combination with 5-Fluorouracil and Irinotecan.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MOFOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to mFOLFOX-6 regime</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MOFOX / Bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Modufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MOFIRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Modufolin in combination with 5-Fluorouracil and Irinotecan</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Modufolin (arfolitixorin)</intervention_name>
    <description>IV injection every second week for 8 weeks.</description>
    <arm_group_label>MOFIRI</arm_group_label>
    <arm_group_label>MOFOX</arm_group_label>
    <arm_group_label>MOFOX / Bevacizumab</arm_group_label>
    <arm_group_label>Modufolin / Nordic FLIRI</arm_group_label>
    <arm_group_label>Modufolin / Nordic FLOX</arm_group_label>
    <arm_group_label>Modufolin / Nordic FLV</arm_group_label>
    <other_name>[6R] 5,10-methylenetetrahydrofolate</other_name>
    <other_name>6R-MTHF</other_name>
    <other_name>6R-methylene THF</other_name>
    <other_name>ISO-901</other_name>
    <other_name>arfolitixorin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorouracil</intervention_name>
    <description>IV injection every second week for 8 weeks.</description>
    <arm_group_label>MOFIRI</arm_group_label>
    <arm_group_label>MOFOX</arm_group_label>
    <arm_group_label>MOFOX / Bevacizumab</arm_group_label>
    <arm_group_label>Modufolin / Nordic FLIRI</arm_group_label>
    <arm_group_label>Modufolin / Nordic FLOX</arm_group_label>
    <arm_group_label>Modufolin / Nordic FLV</arm_group_label>
    <other_name>5-FU</other_name>
    <other_name>5-Flourouacil</other_name>
    <other_name>5-Fluoro-1H,3H-pyrimidine-2,4-dione</other_name>
    <other_name>Adrucil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>IV infusion every second week for 8 weeks.</description>
    <arm_group_label>MOFOX</arm_group_label>
    <arm_group_label>MOFOX / Bevacizumab</arm_group_label>
    <arm_group_label>Modufolin / Nordic FLOX</arm_group_label>
    <other_name>Eloxatin</other_name>
    <other_name>[(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II)</other_name>
    <other_name>Olatin</other_name>
    <other_name>Oxamed</other_name>
    <other_name>Oxitropic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>IV infusion every second week for 8 weeks.</description>
    <arm_group_label>MOFIRI</arm_group_label>
    <arm_group_label>Modufolin / Nordic FLIRI</arm_group_label>
    <other_name>(+)-(4S)-4,11-Dietyl-4-hydroxi-9-[(4-piperidinopiperidino)karbonyloxi]-1H-pyrano[3¢,4¢:6,7]indolizino[1,2-b]kinolin-3,14-(4H,12H)dion</other_name>
    <other_name>Irinosor</other_name>
    <other_name>Campto</other_name>
    <other_name>Namedica</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>IV infusion every second week for 8 weeks.</description>
    <arm_group_label>MOFOX / Bevacizumab</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Advanced metastatic colorectal (Stage IV) cancer verified by biopsy&#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>Göran Carlsson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sahlgrenska University Hospital, Sweden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Odense University Hospital</name>
      <address>
        <city>Odense</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>251 General Airforce Hospital</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical School University of Athens, Aretaieio Hospital</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metropolitan General Hospital</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Genral Hospital Attikon</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Heraklion</name>
      <address>
        <city>Iráklion</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital - Radiumhospitalet</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital - Ullevål</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska University Hospital</name>
      <address>
        <city>Göteborg</city>
        <zip>461 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skaraborg hospital</name>
      <address>
        <city>Skövde</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Greece</country>
    <country>Norway</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>September 7, 2020</last_update_submitted>
  <last_update_submitted_qc>September 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Colorectal cancer</keyword>
  <keyword>Colorectal carcinoma</keyword>
  <keyword>Colorectal tumors</keyword>
  <keyword>Intestinal Neoplasm</keyword>
  <keyword>Gastrointestinal Neoplasm</keyword>
  <keyword>Gastrointestinal disease</keyword>
  <keyword>5,10-methylenetetrahydrofolate</keyword>
  <keyword>Tetrahydrofolates</keyword>
  <keyword>Therapeutic uses</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Pharmacodynamics</keyword>
  <keyword>Safety assessments</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</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/NCT02244632
org study id: ISO-CC-005
secondary id: 2014-001862-84
nct id: NCT02244632
lead sponsor: 
has dmc: No
The purpose is to characterise the tolerability of Modufolin (arfolitixorin) in combination
      with 5-FU alone, in combination with 5-FU and Oxaliplatin, in combination with 5-FU and
      Irinotecan and in combination with 5-FU, Oxaliplatin and Bevacizumab.

      Another purpose is to investigate 4 doses of Modufolin to identify the best dose for further
      assessment.
The study will investigate the tolerability of Modufolin at four (4) different dose levels
      (30 to 240 mg/m2) in therapy combinations with the chemotherapeutic agents 5-FU, Oxaliplatin
      +/- bevcizumab, and Irinotecan.

      When the selected phase 2 dose is determined, 40 additional patients, will be included in the
      study in order to acquire more data on the safety and tolerability of Modufolin at this dose
      level. Twenty (20) of these additional patients will be treated in with Oxaliplatin, 20 with
      Irinotecan.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency and severity of dose limiting toxicity (DLT) or other Adverse Events (AE)
time frame: The patients will be followed during 4 cycles of treatment (8 weeks).
description: Primary safety variables will consist of monitoring and recording of DLTs and any significant AE that have led to adjustments in the therapy administration.
arm group label: Modufolin / Nordic FLV
arm group type: Experimental
description: Modufolin in combination with 5-Fluorouracil only.
arm group label: Modufolin / Nordic FLOX
arm group type: Experimental
description: Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to Nordic FLOX regime
arm group label: Modufolin / Nordic FLIRI
arm group type: Experimental
description: Modufolin in combination with 5-Fluorouracil and Irinotecan.
arm group label: MOFOX
arm group type: Experimental
description: Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to mFOLFOX-6 regime
arm group label: MOFOX / Bevacizumab
arm group type: Experimental
description: Modufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab
arm group label: MOFIRI
arm group type: Experimental
description: Modufolin in combination with 5-Fluorouracil and Irinotecan
intervention type: Drug
intervention name: Modufolin (arfolitixorin)
description: IV injection every second week for 8 weeks.
arm group label: MOFIRI
arm group label: MOFOX
arm group label: MOFOX / Bevacizumab
arm group label: Modufolin / Nordic FLIRI
arm group label: Modufolin / Nordic FLOX
arm group label: Modufolin / Nordic FLV
other name: [6R] 5,10-methylenetetrahydrofolate
other name: 6R-MTHF
other name: 6R-methylene THF
other name: ISO-901
other name: arfolitixorin
intervention type: Drug
intervention name: Fluorouracil
description: IV injection every second week for 8 weeks.
arm group label: MOFIRI
arm group label: MOFOX
arm group label: MOFOX / Bevacizumab
arm group label: Modufolin / Nordic FLIRI
arm group label: Modufolin / Nordic FLOX
arm group label: Modufolin / Nordic FLV
other name: 5-FU
other name: 5-Flourouacil
other name: 5-Fluoro-1H,3H-pyrimidine-2,4-dione
other name: Adrucil
intervention type: Drug
intervention name: Oxaliplatin
description: IV infusion every second week for 8 weeks.
arm group label: MOFOX
arm group label: MOFOX / Bevacizumab
arm group label: Modufolin / Nordic FLOX
other name: Eloxatin
other name: [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II)
other name: Olatin
other name: Oxamed
other name: Oxitropic
intervention type: Drug
intervention name: Irinotecan
description: IV infusion every second week for 8 weeks.
arm group label: MOFIRI
arm group label: Modufolin / Nordic FLIRI
other name: (+)-(4S)-4,11-Dietyl-4-hydroxi-9-[(4-piperidinopiperidino)karbonyloxi]-1H-pyrano[3¢,4¢:6,7]indolizino[1,2-b]kinolin-3,14-(4H,12H)dion
other name: Irinosor
other name: Campto
other name: Namedica
intervention type: Drug
intervention name: Bevacizumab
description: IV infusion every second week for 8 weeks.
arm group label: MOFOX / Bevacizumab
other name: Avastin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Göran Carlsson, MD
role: Principal Investigator
affiliation: Sahlgrenska University Hospital, Sweden
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Greece
country: Norway
country: Sweden
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Colorectal Neoplasms
mesh term: Bevacizumab
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Irinotecan
sharing ipd: No