<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/NCT04450836</url>
  </required_header>
  <id_info>
    <org_study_id>UC-GIG-1910</org_study_id>
    <secondary_id>2019-004196-39</secondary_id>
    <secondary_id>PRODIGE 68 - UCGI 38</secondary_id>
    <nct_id>NCT04450836</nct_id>
  </id_info>
  <brief_title>Sequences Of REGorafenib And Trifluridine/Tipiracil in Patients With Metastatic Colorectal Cancer</brief_title>
  <acronym>SOREGATT</acronym>
  <official_title>A Randomized, Phase II Study Comparing the Sequences of Regorafenib and Trifluridine/Tipiracil, After Failure of Standard Therapies in Patients With Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNICANCER</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>UNICANCER</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized, phase II study comparing the sequences of regorafenib and&#xD;
      trifluridine/tipiracil, after failure of standard therapies in patients with metastatic&#xD;
      colorectal cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicenter, international, comparative, randomized, open-label, phase II study conducted in&#xD;
      two parallel groups.&#xD;
&#xD;
      The study population will consist of male and female patients aged ≥18 years old with&#xD;
      metastatic colorectal cancer after failure of fluoropyrimidine-, irinotecan-, and&#xD;
      oxaliplatin-based chemotherapies, as well as epidermal growth factor receptor (EGFR) and&#xD;
      vascular endothelial growth factor (VEGF) inhibitors in patients eligible for these&#xD;
      treatments.&#xD;
&#xD;
      Patients will be randomized according to a 1:1 ratio to treatment arms A and B.&#xD;
&#xD;
        -  Arm A: regorafenib until disease progression or unacceptable toxicity occurs, followed&#xD;
           by trifluridine/tipiracil until disease progression or unacceptable toxicity occurs.&#xD;
&#xD;
        -  Arm B: trifluridine/tipiracil until disease progression or unacceptable toxicity occurs,&#xD;
           followed by regorafenib until disease progression or unacceptable toxicity occurs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 23, 2020</start_date>
  <completion_date type="Anticipated">May 23, 2028</completion_date>
  <primary_completion_date type="Anticipated">November 23, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the feasibility of treatment sequence (R-TT or TT-R)</measure>
    <time_frame>Expected duration of 5 months from randomization</time_frame>
    <description>The feasibility of the treatment sequence is defined as the percentage of subjects able to receive both regorafenib and trifluridine/tipiracil according to the sequence in 3rd and 4th line. Subjects will be considered as having received both 3rd and 4th lines if they are administered at least two cycles of each line of therapy, i.e. percentage of patients being treated until the first tumor evaluation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of Overall Survival rate</measure>
    <time_frame>Expected duration of 9 months from randomization</time_frame>
    <description>Overall Survival (OS) is defined as the time interval from randomization until death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the progression-free Survival 1 (PFS1)</measure>
    <time_frame>Expected duration of 3 months from randomization</time_frame>
    <description>Progression-free survival 1 (PFS1) is defined as the time interval from randomization until death or the disease progression observed in the first sequence of treatment in each arm, evaluated using Response evaluation criteria in solid tumors (RECIST) v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Progression-free survival 2 (PFS2)</measure>
    <time_frame>Expected duration of 6 months from randomization</time_frame>
    <description>Progression-free survival 2 (PFS2) is defined as the time interval from randomization until death or the disease progression is observed in the later sequence of treatment in each arm, evaluated using RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Disease control rate (DCR)</measure>
    <time_frame>Expected duration of 6 months from randomization</time_frame>
    <description>Disease control rate (DCR) is defined as percentage of patients with a best response that is not progressive disease (PD) (either complete response [CR], partial response [PR], or stable disease [SD]) during treatment. DCR will be assessed in each study arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Objective response rate (ORR)</measure>
    <time_frame>Expected duration of 6 months from randomization</time_frame>
    <description>Objective response rate (ORR) is defined as percentage of patients with a best response being either complete response [CR] or partial response [PR] during treatment. ORR will be assessed in each study arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Time-to-treatment failure 1 (TTF1)</measure>
    <time_frame>Expected duration of 3 months from randomization</time_frame>
    <description>Time-to-treatment failure 1 (TTF1) is defined as the time from randomization to treatment discontinuation for any reason (including disease progression, treatment toxicity, patient preference, or death) during the first sequence of treatment in each arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Time-to-treatment failure 2 (TTF2)</measure>
    <time_frame>Expected duration of 6 months from randomization</time_frame>
    <description>Time-to-treatment failure 2 (TTF2) is defined as the time from randomization to treatment discontinuation for any reason (including disease progression, treatment toxicity, patient preference, or death) during the second sequence of treatment in each arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the health-related quality of life of cancer patients during treatment</measure>
    <time_frame>Expected 30 days after last study treatment administration, up to 5 years</time_frame>
    <description>Quality of life data using the patient reported outcomes, quality of life questionnaire - Core 30 (QLQ-C30) version 3.0 will be collected during the study.&#xD;
Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.&#xD;
The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.&#xD;
All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the performance status deterioration</measure>
    <time_frame>Expected 30 days after last study treatment administration, up to 5 years</time_frame>
    <description>The time to Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 deterioration is defined as the time interval between randomization and the first documented ECOG PS ≥2 during the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the safety (Treatment-Emergent Adverse Events) during treatment</measure>
    <time_frame>Expected 30 days after last study treatment administration, up to 5 years</time_frame>
    <description>Data concerning adverse events graded using the common terminology criteria for adverse events (CTCAE) v5.0 will be collected during the study.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">340</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A (R-TT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Regorafenib followed by trifluridine-tipiracil.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (TT-R)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trifluridine-tipiracil followed by Regorafenib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Regorafenib then Trifluridine/Tipiracil</intervention_name>
    <description>REGORAFENIB 160 mg per day during 3 weeks followed by 1 week off of each 4-week cycle except for cycle 1.&#xD;
During first cycle: dose is started at 80 mg per day at week 1, 120 mg per day at week 2, 160 mg per day at week 3, followed by 1 week off.&#xD;
Then TRIFLURIDINE/TIPIRACIL 35 mg/m² Dose administered orally twice daily on Days 1 to 5 and Days 8 to 12 of each 4-week cycle.</description>
    <arm_group_label>Arm A (R-TT)</arm_group_label>
    <other_name>STIVARGA</other_name>
    <other_name>LONSURF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trifluridine/Tipiracil then Regorafenib</intervention_name>
    <description>TRIFLURIDINE/TIPIRACIL 35 mg/m² Dose administered orally twice daily on Days 1 to 5 and Days 8 to 12 of each 4-week cycle.&#xD;
Then REGORAFENIB 160 mg per day during 3 weeks followed by 1 week off of each 4-week cycle except for cycle 1.&#xD;
During first cycle: dose is started at 80 mg per day at week 1, 120 mg per day at week 2, 160 mg per day at week 3, followed by 1 week off.</description>
    <arm_group_label>Arm B (TT-R)</arm_group_label>
    <other_name>LONSURF</other_name>
    <other_name>STIVARGA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have provided informed consent before performing any study specific&#xD;
             procedures.&#xD;
&#xD;
          2. Histological or cytological documented adenocarcinoma of the colon or rectum.&#xD;
&#xD;
          3. Patients with metastatic colorectal cancer (stage IV).&#xD;
&#xD;
          4. Measurable disease, defined as at least one unidimensional measurable lesion on a&#xD;
             computed tomography (CT) scan according to RECIST v1.1.&#xD;
&#xD;
          5. The patient must have progressed following exposure of all the following agents : one&#xD;
             fluoropyrimidine-based chemotherapy (capecitabine or fluorouracil [5-FU], combined&#xD;
             with oxaliplatin and/or irinotecan (including FOLFOX, FOLFIRI or FOLFOXIRI) as well as&#xD;
             EGFR and/or VEGF inhibitors in patients eligible for these treatments.&#xD;
&#xD;
          6. Patients considered eligible for treatment with both regorafenib and&#xD;
             trifluridine-tipiracil.&#xD;
&#xD;
          7. Male or female patients aged ≥18 years.&#xD;
&#xD;
          8. ECOG performance status of ≤1.&#xD;
&#xD;
          9. Adequate bone marrow, liver and renal functions as assessed by the following&#xD;
             laboratory requirements:&#xD;
&#xD;
               -  Total bilirubin ≤1.5 x upper limit of normal (ULN).&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN&#xD;
                  (≤5 x ULN for patients with liver metastasis).&#xD;
&#xD;
               -  Alkaline phosphatase limit ≤2.5 x ULN (≤5 x ULN for patients with liver&#xD;
                  metastasis).&#xD;
&#xD;
               -  Serum creatinine ≤1.5 x ULN.&#xD;
&#xD;
               -  International normalized ratio (INR) and partial thromboplastin time (PTT) ≤1.5 x&#xD;
                  ULN. Patients receiving anticoagulants, such as warfarin or heparin are eligible&#xD;
                  if there is no prior evidence of an underlying abnormality with coagulation.&#xD;
&#xD;
               -  Platelet count ≥75000 /mm³, hemoglobin (Hb) ≥9 g/dL, absolute neutrophil count&#xD;
                  (ANC) ≥1500/mm³. Blood transfusions to meet this inclusion criterion are not&#xD;
                  allowed.&#xD;
&#xD;
         10. Women of childbearing potential and men must agree to use a highly effective&#xD;
             contraception (1% failure rate) from the signing of the informed consent form until at&#xD;
             least 6 months after the last study drug administration. Women using hormonal&#xD;
             contraceptive must also use a barrier method.&#xD;
&#xD;
         11. Women of childbearing potential must have a negative pregnancy test within 7 days&#xD;
             before starting study treatment.&#xD;
&#xD;
         12. Patients affiliated to the social security system.&#xD;
&#xD;
         13. Patient willing and able to comply with the protocol for the duration of the study&#xD;
             including treatment, scheduled visits, and examinations throughout the study,&#xD;
             including follow up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with symptomatic brain or meningeal metastasis, unless definitive therapy&#xD;
             occurred more than 6 months ago and with a confirmation of tumoral control within 4&#xD;
             weeks of starting study treatment.&#xD;
&#xD;
          2. Previous or concurrent cancer that is distinct in primary site or histology from&#xD;
             colorectal cancer within 5 years prior to study inclusion, except for curatively&#xD;
             treated in situ cervical cancer, non-melanoma skin cancer, and superficial bladder&#xD;
             tumors: staged Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor with&#xD;
             lamina propria invasion).&#xD;
&#xD;
          3. Prior treatment with regorafenib or any other tyrosine kinase inhibitor.&#xD;
&#xD;
          4. Prior treatment with trifluridine/tipiracil.&#xD;
&#xD;
          5. Known hypersensitivity to any of the study drugs, study drug classes, or study drug&#xD;
             excipients.&#xD;
&#xD;
          6. Unresolved toxicity grade &gt;1 (by CTCAE v5.0) caused by prior therapy/procedure,&#xD;
             excluding alopecia, hypothyroidism, and oxaliplatin-induced neurotoxicity grade ≤2.&#xD;
&#xD;
          7. Patient with moderate or severe hepatic impairment (Child-Pugh C).&#xD;
&#xD;
          8. Known UGT1A1 polymorphisms. History of Gilbert's syndrome.&#xD;
&#xD;
          9. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days&#xD;
             before starting study treatment.&#xD;
&#xD;
         10. Chemotherapy within 21 days of starting study treatment.&#xD;
&#xD;
         11. Radiotherapy within 4 weeks of starting study treatment, except for palliative&#xD;
             radiotherapy within 2 weeks.&#xD;
&#xD;
         12. Active cardiac disease including any of the Following:&#xD;
&#xD;
               -  Congestive heart Failure: New York Heart Association (NYHA) class ≥2.&#xD;
&#xD;
               -  Unstable angina (angina symptoms at rest), or a new-onset angina (within the 3&#xD;
                  months before enrolment).&#xD;
&#xD;
               -  Myocardial infarction that occurred less than 6 months before enrolment.&#xD;
&#xD;
               -  Cardiac arrhythmias requiring anti-arrhythmic therapy (treatment with beta&#xD;
                  blockers or digoxin are permitted)&#xD;
&#xD;
               -  Uncontrolled hypertension (systolic blood pressure &gt;140 mmHg or diastolic&#xD;
                  pressure &gt;90 mmHg despite treatment).&#xD;
&#xD;
         13. Arterial or venous thrombotic or embolic events such as cerebrovascular accident&#xD;
             (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism&#xD;
             within 6 months of starting study treatment.&#xD;
&#xD;
         14. Ongoing infection grade 2 (CTCAE v5.0).&#xD;
&#xD;
         15. Known history of human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
         16. Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with&#xD;
             antiviral therapy.&#xD;
&#xD;
         17. Patients with seizure disorder requiring medication.&#xD;
&#xD;
         18. Patients with a history of any bleeding diathesis, irrespective of the severity.&#xD;
&#xD;
         19. Any hemorrhage or bleeding event grade ≥3 (CTCAE v5.0) within 4 weeks before starting&#xD;
             study treatment.&#xD;
&#xD;
         20. Presence of a wound, ulcer, or bone fracture that is not healing.&#xD;
&#xD;
         21. Patients unable to swallow oral medications.&#xD;
&#xD;
         22. Bowel malabsorption or extended bowel resection that could affect the absorption of&#xD;
             regorafenib, occlusive syndrome.&#xD;
&#xD;
         23. Presence of gastro-intestinal fistula or perforation.&#xD;
&#xD;
         24. Any illness or medical conditions that are unstable or could jeopardize the safety of&#xD;
             the patient and their compliance in the study.&#xD;
&#xD;
         25. Patients participating in another therapeutic study within the 30 days before&#xD;
             enrolment.&#xD;
&#xD;
         26. Pregnant or breast feeding women.&#xD;
&#xD;
         27. Person deprived of their liberty or under protective custody or guardianship.&#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>Michel MD DUCREUX, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gustave Roussy, Cancer Campus, Grand Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Florence GARIC, Pharm D</last_name>
    <phone>0033171936707</phone>
    <email>f-garic@unicancer.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Clinique Saint Luc</name>
      <address>
        <city>Bouge</city>
        <zip>5004</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Marie MAILLEUX, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH de l'Ardenne</name>
      <address>
        <city>Libramont</city>
        <zip>6800</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Frederic FORGET, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Verviers</name>
      <address>
        <city>Verviers</city>
        <zip>4800</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Hassan KALANTARI, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Privé Pays de Savoie</name>
      <address>
        <city>Annemasse</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Wulfran CACHEUX, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier d'Auxerre</name>
      <address>
        <city>Auxerre</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Anne-Laure VILLING, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Sainte Catherine</name>
      <address>
        <city>Avignon</city>
        <zip>84000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Isabelle MARTINEZ</last_name>
    </contact>
    <investigator>
      <last_name>Clemence TOULLEC, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Bayeux</name>
      <address>
        <city>Bayeux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Annie PEYTIER, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre François Baclesse</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Aurélie PARZY, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Infirmerie Protestante de Lyon</name>
      <address>
        <city>Caluire-et-Cuire</city>
        <zip>69300</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Hervé PERRIER</last_name>
    </contact>
    <investigator>
      <last_name>William DRONNE, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Trousseau</name>
      <address>
        <city>Chambray-lès-Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>CH Cotentin</name>
      <address>
        <city>Cherbourg</city>
        <zip>50102</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Amr EL WESHI, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Bourgogne</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cyrielle MAISSIAT</last_name>
      <email>cmaissiat@icb-cancer.fr</email>
    </contact>
    <investigator>
      <last_name>Véronique LORGIS, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Diane PANNIER, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Scorff</name>
      <address>
        <city>Lorient</city>
        <zip>56322</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nolwen LEISSEN</last_name>
      <email>n.leissen@ghbs.bzh</email>
    </contact>
    <investigator>
      <last_name>Caroline COUFFON, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Clélia COUTZAC, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Association Hôpital Saint Joseph de Marseille</name>
      <address>
        <city>Marseille</city>
        <zip>13008</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christophe LAPLACE</last_name>
      <email>claplace@hopital-saint-joseph.fr</email>
    </contact>
    <investigator>
      <last_name>Hervé PERRIER, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Timone</name>
      <address>
        <city>Marseille</city>
        <zip>13365</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Hôpital privé du Confluent</name>
      <address>
        <city>Nantes</city>
        <zip>44277</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carole LENNE</last_name>
      <email>carole.LENNE@groupeconfluent.fr</email>
    </contact>
    <investigator>
      <last_name>Hélène CASTANIE, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Antoine Lacassagne</name>
      <address>
        <city>Nice</city>
        <zip>06189</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Aude Dabadie</last_name>
      <email>Aude.DABADIE@nice.unicancer.fr</email>
    </contact>
    <investigator>
      <last_name>Ludovic EVESQUE, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Privé des Peupliers</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ibtissam CHABANE</last_name>
      <email>i.chabane@ramsaygds.fr</email>
    </contact>
    <investigator>
      <last_name>Mustapha ZOUBIR, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>APHP - Hôpital Européen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Julien TAIEB, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Groupe hospitalier Pitié Salpétrière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Jean-Baptiste BACHET, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Périgueux</name>
      <address>
        <city>Perigueux</city>
        <zip>24000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Marie AUGIS</last_name>
      <email>marie.augis@ch-perigueux.fr</email>
    </contact>
    <investigator>
      <last_name>Florbela GRILO DIAS, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Saint Jean</name>
      <address>
        <city>Perpignan</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Faiza KHEMISSA, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Bordeaux - Hôpital Haut Lévèque</name>
      <address>
        <city>Pessac</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Denis SMITH, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Privé des Côtes d'Armor - Centre CARIO-HPCA</name>
      <address>
        <city>Plérin</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Jérôme MARIN BABAU, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Poitiers</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David TOUGERON</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU - Robert Debre</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Olivier BOUCHE, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Jean Godinot</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Damien BOTSEN</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopital Charles Nicolle</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>David SEFRIOUI</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Saint Malo</name>
      <address>
        <city>Saint-Malo</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Juliette VIAUD, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Hôpital Nord</name>
      <address>
        <city>Saint-Étienne</city>
        <zip>42270</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabrice DI PALMA</last_name>
      <email>fabrice.dipalma@chu-st-etienne.fr</email>
    </contact>
    <investigator>
      <last_name>Jean-Marc PHELIP, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Paul Strauss (ICANS)</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Meher BEN ABDELGHANI, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Toulouse</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Quentin PANOUILLE</last_name>
      <email>panouille.q@chu-toulouse.fr</email>
    </contact>
    <contact_backup>
      <last_name>Rosine GUIMBAUD, Dr</last_name>
      <email>guimbaud.r@chu-toulouse.fr</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Valence</name>
      <address>
        <city>Valence</city>
        <zip>26000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marine BAUDIN</last_name>
      <email>mbaudin@ch-valence.fr</email>
    </contact>
    <investigator>
      <last_name>Nicolas ETCHEPARE, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Lorraine</name>
      <address>
        <city>Vandoeuvre Les Nancy</city>
        <zip>54519</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Pierre LEHAIR, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Paul Brousse</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Elise COLLE, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Michel DUCREUX, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>December 14, 2022</last_update_submitted>
  <last_update_submitted_qc>December 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Regorafenib</keyword>
  <keyword>Trifluridine/Tipiracil</keyword>
  <keyword>Metastatic colorectal cancer</keyword>
  <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>Trifluridine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04450836
org study id: UC-GIG-1910
secondary id: 2019-004196-39
secondary id: PRODIGE 68 - UCGI 38
nct id: NCT04450836
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A randomized, phase II study comparing the sequences of regorafenib and
      trifluridine/tipiracil, after failure of standard therapies in patients with metastatic
      colorectal cancer
Multicenter, international, comparative, randomized, open-label, phase II study conducted in
      two parallel groups.

      The study population will consist of male and female patients aged ≥18 years old with
      metastatic colorectal cancer after failure of fluoropyrimidine-, irinotecan-, and
      oxaliplatin-based chemotherapies, as well as epidermal growth factor receptor (EGFR) and
      vascular endothelial growth factor (VEGF) inhibitors in patients eligible for these
      treatments.

      Patients will be randomized according to a 1:1 ratio to treatment arms A and B.

        -  Arm A: regorafenib until disease progression or unacceptable toxicity occurs, followed
           by trifluridine/tipiracil until disease progression or unacceptable toxicity occurs.

        -  Arm B: trifluridine/tipiracil until disease progression or unacceptable toxicity occurs,
           followed by regorafenib until disease progression or unacceptable toxicity occurs.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To evaluate the feasibility of treatment sequence (R-TT or TT-R)
time frame: Expected duration of 5 months from randomization
description: The feasibility of the treatment sequence is defined as the percentage of subjects able to receive both regorafenib and trifluridine/tipiracil according to the sequence in 3rd and 4th line. Subjects will be considered as having received both 3rd and 4th lines if they are administered at least two cycles of each line of therapy, i.e. percentage of patients being treated until the first tumor evaluation.
measure: To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of Overall Survival rate
time frame: Expected duration of 9 months from randomization
description: Overall Survival (OS) is defined as the time interval from randomization until death from any cause.
measure: To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the progression-free Survival 1 (PFS1)
time frame: Expected duration of 3 months from randomization
description: Progression-free survival 1 (PFS1) is defined as the time interval from randomization until death or the disease progression observed in the first sequence of treatment in each arm, evaluated using Response evaluation criteria in solid tumors (RECIST) v1.1.
measure: To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Progression-free survival 2 (PFS2)
time frame: Expected duration of 6 months from randomization
description: Progression-free survival 2 (PFS2) is defined as the time interval from randomization until death or the disease progression is observed in the later sequence of treatment in each arm, evaluated using RECIST v1.1.
measure: To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Disease control rate (DCR)
time frame: Expected duration of 6 months from randomization
description: Disease control rate (DCR) is defined as percentage of patients with a best response that is not progressive disease (PD) (either complete response [CR], partial response [PR], or stable disease [SD]) during treatment. DCR will be assessed in each study arm.
measure: To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Objective response rate (ORR)
time frame: Expected duration of 6 months from randomization
description: Objective response rate (ORR) is defined as percentage of patients with a best response being either complete response [CR] or partial response [PR] during treatment. ORR will be assessed in each study arm.
measure: To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Time-to-treatment failure 1 (TTF1)
time frame: Expected duration of 3 months from randomization
description: Time-to-treatment failure 1 (TTF1) is defined as the time from randomization to treatment discontinuation for any reason (including disease progression, treatment toxicity, patient preference, or death) during the first sequence of treatment in each arm.
measure: To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Time-to-treatment failure 2 (TTF2)
time frame: Expected duration of 6 months from randomization
description: Time-to-treatment failure 2 (TTF2) is defined as the time from randomization to treatment discontinuation for any reason (including disease progression, treatment toxicity, patient preference, or death) during the second sequence of treatment in each arm.
measure: To evaluate the health-related quality of life of cancer patients during treatment
time frame: Expected 30 days after last study treatment administration, up to 5 years
description: Quality of life data using the patient reported outcomes, quality of life questionnaire - Core 30 (QLQ-C30) version 3.0 will be collected during the study.
Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.
The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.
All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
measure: To evaluate the performance status deterioration
time frame: Expected 30 days after last study treatment administration, up to 5 years
description: The time to Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 deterioration is defined as the time interval between randomization and the first documented ECOG PS ≥2 during the study.
measure: To evaluate the safety (Treatment-Emergent Adverse Events) during treatment
time frame: Expected 30 days after last study treatment administration, up to 5 years
description: Data concerning adverse events graded using the common terminology criteria for adverse events (CTCAE) v5.0 will be collected during the study.
arm group label: Arm A (R-TT)
arm group type: Experimental
description: Regorafenib followed by trifluridine-tipiracil.
arm group label: Arm B (TT-R)
arm group type: Experimental
description: Trifluridine-tipiracil followed by Regorafenib.
intervention type: Drug
intervention name: Regorafenib then Trifluridine/Tipiracil
description: REGORAFENIB 160 mg per day during 3 weeks followed by 1 week off of each 4-week cycle except for cycle 1.
During first cycle: dose is started at 80 mg per day at week 1, 120 mg per day at week 2, 160 mg per day at week 3, followed by 1 week off.
Then TRIFLURIDINE/TIPIRACIL 35 mg/m² Dose administered orally twice daily on Days 1 to 5 and Days 8 to 12 of each 4-week cycle.
arm group label: Arm A (R-TT)
other name: STIVARGA
other name: LONSURF
intervention type: Drug
intervention name: Trifluridine/Tipiracil then Regorafenib
description: TRIFLURIDINE/TIPIRACIL 35 mg/m² Dose administered orally twice daily on Days 1 to 5 and Days 8 to 12 of each 4-week cycle.
Then REGORAFENIB 160 mg per day during 3 weeks followed by 1 week off of each 4-week cycle except for cycle 1.
During first cycle: dose is started at 80 mg per day at week 1, 120 mg per day at week 2, 160 mg per day at week 3, followed by 1 week off.
arm group label: Arm B (TT-R)
other name: LONSURF
other name: STIVARGA
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michel MD DUCREUX, Pr
role: Principal Investigator
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
last name: Florence GARIC, Pharm D
phone: 0033171936707
email: f-garic@unicancer.fr
facility: 
status: Recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
country: Belgium
country: France
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Trifluridine