<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/NCT04431258</url>
  </required_header>
  <id_info>
    <org_study_id>ABT-C11-2020</org_study_id>
    <secondary_id>2020-002791-13</secondary_id>
    <secondary_id>FD-R-006817-01</secondary_id>
    <nct_id>NCT04431258</nct_id>
  </id_info>
  <brief_title>ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study</brief_title>
  <acronym>PanC-ASAP</acronym>
  <official_title>A Phase I Open Label Followed by a Phase II Randomized, Controlled Study to Assess the Efficacy and Safety of ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ability Pharmaceuticals SL</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ability Pharmaceuticals SL</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase I open label followed by a Phase II randomized, controlled study to assess the&#xD;
      efficacy and safety of ABTL0812 in combination with FOLFIRINOX for first-line treatment of&#xD;
      metastatic pancreatic. Funded by: FDA OOPD (Grant #FD-R-006817-01), H2020 EIC Accelerator&#xD;
      (Grant #954825) and Ability Pharmaceuticals SL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase I: This is an open label Phase I to determine the RP2D of ABTL0812 in combination with&#xD;
      FOLFIRINOX. All patients will receive ABTL0812 in combination with FOLFIRINOX.&#xD;
&#xD;
      A dose de-escalation phase will be performed in which up to 3 different ABTL0812 dose levels&#xD;
      will be tested in combination with FOLFIRINOX. ABTL0812 doses are: 1300 mg tid (starting&#xD;
      dose), followed (if necessary) by 975 mg tid and 650 mg tid. Patient intra-escalation is not&#xD;
      allowed.&#xD;
&#xD;
      Phase II: This is a double blind, randomized, placebo-controlled Phase II multicenter study&#xD;
      to evaluate ABTL0812 in combination with FOLFIRINOX for first-line treatment of metastatic&#xD;
      pancreatic cancer. Patients will be randomized to one of two groups: arm A) receiving&#xD;
      ABTL0812 in addition to FOLFIRINOX and arm B) receiving FOLFIRINOX plus placebo.&#xD;
&#xD;
      Arm A) ABTL0812 + FOLFIRINOX Arm B) PLACEBO + FOLFIRINOX&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 6, 2021</start_date>
  <completion_date type="Anticipated">September 1, 2028</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2024</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Double blind, randomized, placebo-controlled, multicenter study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase I - RP2D</measure>
    <time_frame>5 weeks</time_frame>
    <description>Recommended Phase II Dose (RP2D) of ABTL0812 in combination with FOLFIRINOX</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase II - PFS</measure>
    <time_frame>1 year</time_frame>
    <description>PFS using RECIST v1.1 by central review</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>1 year</time_frame>
    <description>PFS using RECIST v1.1 by investigator analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>1 year</time_frame>
    <description>Objective response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS 6 m</measure>
    <time_frame>6 months</time_frame>
    <description>PFS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTR</measure>
    <time_frame>1 year</time_frame>
    <description>Time to response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR</measure>
    <time_frame>1 year</time_frame>
    <description>Duration of response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>5 years</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS 1y</measure>
    <time_frame>1 year</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants with Adverse Events (AE). AEs classified according to CTCAE v5.0</description>
  </secondary_outcome>
  <other_outcome>
    <measure>PK - Cmax</measure>
    <time_frame>1 month</time_frame>
    <description>Determination of peak plasma concentration</description>
  </other_outcome>
  <other_outcome>
    <measure>PK - AUC</measure>
    <time_frame>1 month</time_frame>
    <description>Determinatoin of Area under the plasma concentration versus time curve</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of Life Questionnaire QLC-C30</measure>
    <time_frame>1 year</time_frame>
    <description>Quality of life measured with questionnaires QLC-C30</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of Life Questionnaire QLQ-PAN26</measure>
    <time_frame>1 year</time_frame>
    <description>Quality of life measured with questionnaires QLQ-PAN26</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A) ABTL0812 + FOLFIRINOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FOLFIRINOX will be dosed according to the standard following regimen:&#xD;
oxaliplatin 85 mg/m2, administered as 2-hour iv infusion&#xD;
leucovorin 400 mg/m2, administered as 2-hour iv infusion&#xD;
irinotecan 180 mg/m2, administered as 1.5-hour iv infusion&#xD;
fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities.&#xD;
ABTL0812 will be administered daily at its RP2D. ABTL0812 will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, ABTL0812 will be maintained once chemotherapy is discontinued, if ABTL0812 is tolerated and if the patient is in response or stable disease.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B) PLACEBO + FOLFIRINOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FOLFIRINOX will be dosed according to the standard following regimen:&#xD;
oxaliplatin 85 mg/m2, administered as 2-hour iv infusion&#xD;
leucovorin 400 mg/m2, administered as 2-hour iv infusion&#xD;
irinotecan 180 mg/m2, administered as 1.5-hour iv infusion&#xD;
fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities.&#xD;
Placebo will be administered at the same volume than ABTL0812 in arm A) FOLFIRINOX, then daily during chemotherapy cycles. Also, placebo will be maintained once chemotherapy is discontinued.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ABTL0812</intervention_name>
    <description>ABTL0812 will be administered daily at its RP2D. ABTL0812 will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, ABTL0812 will be maintained once chemotherapy is discontinued, if ABTL0812 is tolerated and if the patient is in response or stable disease.</description>
    <arm_group_label>Arm A) ABTL0812 + FOLFIRINOX</arm_group_label>
    <arm_group_label>Arm B) PLACEBO + FOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Folfirinox</intervention_name>
    <description>FOLFIRINOX will be dosed according to the standard following regimen:&#xD;
oxaliplatin 85 mg/m2, administered as 2-hour iv infusion&#xD;
leucovorin 400 mg/m2, administered as 2-hour iv infusion&#xD;
irinotecan 180 mg/m2, administered as 1.5-hour iv infusion&#xD;
fluorouracil 2400 mg/m2, administered as 46-hour iv infusionevery 2 weeks (=1 cycle) until disease progression or unacceptable toxicities.</description>
    <arm_group_label>Arm A) ABTL0812 + FOLFIRINOX</arm_group_label>
    <other_name>Chemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo will be administered daily at the same regim as ABTL0812. Placebo will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, placebo will be maintained once chemotherapy is discontinued, if the patient is in response or stable disease.</description>
    <arm_group_label>Arm B) PLACEBO + FOLFIRINOX</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed carcinoma, adenocarcinoma or ductal&#xD;
             adenocarcinoma of the pancreas.&#xD;
&#xD;
          2. Confirmed metastatic disease&#xD;
&#xD;
          3. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version&#xD;
             1.1 guidelines with at least one &quot;target lesion&quot; to be used to assess response. Tumors&#xD;
             within a previously irradiated field will be designated as &quot;non-target&quot; lesions unless&#xD;
             progression is documented.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.&#xD;
&#xD;
          5. Age, older than 18 years old&#xD;
&#xD;
          6. Adequate hematologic function, measured as:&#xD;
&#xD;
               -  absolute neutrophil count ≥ 1.5x109/L&#xD;
&#xD;
               -  platelet count ≥ 100x109/L without transfusion support&#xD;
&#xD;
               -  hemoglobin ≥ 10 g/dL&#xD;
&#xD;
          7. Total bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
          8. Albumin ≥ 3.3 g/dL&#xD;
&#xD;
          9. AST (SGOT) and ALT (SGPT) ≤ 2.5 times x upper limit of normal (≤ 5 times the ULN in&#xD;
             patients with evidence of liver metastases)&#xD;
&#xD;
         10. Alkaline phosphatase ≤ 2.5 times ULN (≤5 times the ULN in patients with evidence of&#xD;
             liver metastases)&#xD;
&#xD;
         11. Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2&#xD;
&#xD;
         12. Only for Phase II patients. If available, a sample of tumor tissue or cytology (either&#xD;
             archival or new tumor biopsy) for biomarker analyses. The most recently collected&#xD;
             tumor tissue sample should be provided.&#xD;
&#xD;
         13. Contraception: All premenopausal female patients must use contraception. Male patients&#xD;
             and their female partners (if fertile), must use contraception as well. In both cases,&#xD;
             contraception means two forms of highly effective contraception during the study and&#xD;
             for a period of 6 months following the last administration of the study drug.&#xD;
&#xD;
         14. Willing and able to provide informed consent&#xD;
&#xD;
         15. Ability and willingness to comply with study visits, treatment, testing, and to comply&#xD;
             with the protocol.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Patients with any histology other than carcinoma, adenocarcinoma or ductal&#xD;
             adenocarcinoma (such as squamous cell, acinar cell, medullary, colloid,&#xD;
             neuroendocrine, etc)&#xD;
&#xD;
          2. Patients has only locally advanced disease, resectable or borderline resectable.&#xD;
&#xD;
          3. The patient has received chemotherapy as adjuvant therapy for locally advanced&#xD;
             disease, resectable or borderline resectable.&#xD;
&#xD;
          4. Patient has received previous abdominal radiotherapy, (with the exception of analgesic&#xD;
             radiotherapy that was not performed on target lesions).&#xD;
&#xD;
          5. Patients previously treated with an inhibitor of the PI3K/Akt/mTOR pathway by a&#xD;
             systemic route.&#xD;
&#xD;
          6. History of chronic diarrhea or inflammatory disease of the colon or rectum, or&#xD;
             occlusion or sub-occlusion not resolved under symptomatic treatment&#xD;
&#xD;
          7. Patient is pregnant or in lactation period. High sensitivity pregnancy test (urine or&#xD;
             serum) to be performed within 7 days before study treatment starts.&#xD;
&#xD;
          8. Patient had myocardial infarction within ≤ 6 months prior to study entry, LVEF &lt;50%,&#xD;
             symptomatic congestive heart failure (New York Heart Association &gt; class II), unstable&#xD;
             angina pectoris, or unstable cardiac arrhythmia requiring medication.&#xD;
&#xD;
          9. 12-lead ECG with clinically relevant abnormality or showing a QTcF &gt;450 ms, PR &gt;210&#xD;
             ms, or QRS &gt;120 ms at screening.&#xD;
&#xD;
         10. Patients with any other medical conditions (such as psychiatric illness,&#xD;
             cardiovascular disease, infectious diseases, abnormal physical examination or&#xD;
             laboratory findings) that in the opinion of the investigator may interfere with the&#xD;
             planned treatment, affect patient compliance or place the patient at high risk from&#xD;
             treatment-related complications.&#xD;
&#xD;
         11. Patient has active Hepatitis B or C, human immunodeficiency virus (HIV) or Covid-19&#xD;
             infection with non-controlled disease according to the treating physician.&#xD;
&#xD;
         12. Patients unable to provide informed consent like those under administrative or legal&#xD;
             supervision&#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>Marc Cortal</last_name>
    <role>Study Director</role>
    <affiliation>Ability Pharmaceuticals SL</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marc Cortal</last_name>
    <phone>+34603141706</phone>
    <email>contact@abilitypharma.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Kansas Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205-0000</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anup Kasi, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Colin Weekes, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Davendra Sohal</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CGFL Dijon</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>François Ghiringhelli</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institute Paoli-Calmettes</name>
      <address>
        <city>Marseille</city>
        <zip>13009</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emmanuel Mitry</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antoine Hollebecque</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Rabam MC</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Maria Passhak</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Shaare Zedek MC</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Hadas Dresler</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sheba MC</name>
      <address>
        <city>Ramat Gan</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Talia Golan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ICO Badalona</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laura Layos-Romero</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centro Oncológico de Galicia</name>
      <address>
        <city>A Coruña</city>
        <state>Galicia</state>
        <zip>15009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuel Ramos Vázquez</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Dr. Balmis</name>
      <address>
        <city>Alicante</city>
        <zip>03010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bartomeu Massutí Sureda</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Quiron Salud</name>
      <address>
        <city>Barcelona</city>
        <zip>08023</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>José Luis Cuadra</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vall d'Hebron University Hospital</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Teresa Macarulla</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ICO Girona</name>
      <address>
        <city>Girona</city>
        <zip>17007</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adelaida García</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Arnau de Vilanova</name>
      <address>
        <city>Lleida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alberto Rodrigo-Cáceres</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Andrés Muñoz</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Rocío García Carbonero</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Morales Meseguer</name>
      <address>
        <city>Murcia</city>
        <zip>30008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alberto Carmona</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Inmaculada Gallego-Gimenez</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Toledo</name>
      <address>
        <city>Toledo</city>
        <zip>45007</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ignacio García Escobar</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susana Rosello</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roberto Pazo Cid</last_name>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
    <country>Israel</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Erazo T, Lorente M, Lopez-Plana A, Munoz-Guardiola P, Fernandez-Nogueira P, Garcia-Martinez JA, Bragado P, Fuster G, Salazar M, Espadaler J, Hernandez-Losa J, Bayascas JR, Cortal M, Vidal L, Gascon P, Gomez-Ferreria M, Alfon J, Velasco G, Domenech C, Lizcano JM. The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase. Clin Cancer Res. 2016 May 15;22(10):2508-19. doi: 10.1158/1078-0432.CCR-15-1808. Epub 2015 Dec 15.</citation>
    <PMID>26671995</PMID>
  </reference>
  <reference>
    <citation>Munoz-Guardiola P, Casas J, Megias-Roda E, Sole S, Perez-Montoyo H, Yeste-Velasco M, Erazo T, Dieguez-Martinez N, Espinosa-Gil S, Munoz-Pinedo C, Yoldi G, Abad JL, Segura MF, Moran T, Romeo M, Bosch-Barrera J, Oaknin A, Alfon J, Domenech C, Fabrias G, Velasco G, Lizcano JM. The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells. Autophagy. 2021 Jun;17(6):1349-1366. doi: 10.1080/15548627.2020.1761651. Epub 2020 May 25.</citation>
    <PMID>32397857</PMID>
  </reference>
  <reference>
    <citation>Felip I, Moiola CP, Megino-Luque C, Lopez-Gil C, Cabrera S, Sole-Sanchez S, Munoz-Guardiola P, Megias-Roda E, Perez-Montoyo H, Alfon J, Yeste-Velasco M, Santacana M, Dolcet X, Reques A, Oaknin A, Rodriguez-Freixinos V, Lizcano JM, Domenech C, Gil-Moreno A, Matias-Guiu X, Colas E, Eritja N. Therapeutic potential of the new TRIB3-mediated cell autophagy anticancer drug ABTL0812 in endometrial cancer. Gynecol Oncol. 2019 May;153(2):425-435. doi: 10.1016/j.ygyno.2019.03.002. Epub 2019 Mar 7.</citation>
    <PMID>30853360</PMID>
  </reference>
  <reference>
    <citation>Lopez-Plana A, Fernandez-Nogueira P, Munoz-Guardiola P, Sole-Sanchez S, Megias-Roda E, Perez-Montoyo H, Jauregui P, Yeste-Velasco M, Gomez-Ferreria M, Erazo T, Ametller E, Recalde-Percaz L, Moragas-Garcia N, Noguera-Castells A, Mancino M, Moran T, Nadal E, Alfon J, Domenech C, Gascon P, Lizcano JM, Fuster G, Bragado P. The novel proautophagy anticancer drug ABTL0812 potentiates chemotherapy in adenocarcinoma and squamous nonsmall cell lung cancer. Int J Cancer. 2020 Aug 15;147(4):1163-1179. doi: 10.1002/ijc.32865. Epub 2020 Feb 6.</citation>
    <PMID>31943158</PMID>
  </reference>
  <reference>
    <citation>Vidal L, Victoria I, Gaba L, Martin MG, Brunet M, Colom H, Cortal M, Gomez-Ferreria M, Yeste-Velasco M, Perez A, Rodon J, Sohal DPS, Lizcano JM, Domenech C, Alfon J, Gascon P. A first-in-human phase I/Ib dose-escalation clinical trial of the autophagy inducer ABTL0812 in patients with advanced solid tumours. Eur J Cancer. 2021 Mar;146:87-94. doi: 10.1016/j.ejca.2020.12.019. Epub 2021 Feb 12.</citation>
    <PMID>33588149</PMID>
  </reference>
  <reference>
    <citation>Paris-Coderch L, Soriano A, Jimenez C, Erazo T, Munoz-Guardiola P, Masanas M, Antonelli R, Boloix A, Alfon J, Perez-Montoyo H, Yeste-Velasco M, Domenech C, Roma J, Sanchez de Toledo J, Moreno L, Lizcano JM, Gallego S, Segura MF. The antitumour drug ABTL0812 impairs neuroblastoma growth through endoplasmic reticulum stress-mediated autophagy and apoptosis. Cell Death Dis. 2020 Sep 17;11(9):773. doi: 10.1038/s41419-020-02986-w.</citation>
    <PMID>32943619</PMID>
  </reference>
  <reference>
    <citation>Mancini A, Colapietro A, Cristiano L, Rossetti A, Mattei V, Gravina GL, Perez-Montoyo H, Yeste-Velasco M, Alfon J, Domenech C, Festuccia C. Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models. Front Oncol. 2022 Nov 2;12:943064. doi: 10.3389/fonc.2022.943064. eCollection 2022.</citation>
    <PMID>36408162</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>July 13, 2023</last_update_submitted>
  <last_update_submitted_qc>July 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folfirinox</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/NCT04431258
org study id: ABT-C11-2020
secondary id: 2020-002791-13
secondary id: FD-R-006817-01
nct id: NCT04431258
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A Phase I open label followed by a Phase II randomized, controlled study to assess the
      efficacy and safety of ABTL0812 in combination with FOLFIRINOX for first-line treatment of
      metastatic pancreatic. Funded by: FDA OOPD (Grant #FD-R-006817-01), H2020 EIC Accelerator
      (Grant #954825) and Ability Pharmaceuticals SL.
Phase I: This is an open label Phase I to determine the RP2D of ABTL0812 in combination with
      FOLFIRINOX. All patients will receive ABTL0812 in combination with FOLFIRINOX.

      A dose de-escalation phase will be performed in which up to 3 different ABTL0812 dose levels
      will be tested in combination with FOLFIRINOX. ABTL0812 doses are: 1300 mg tid (starting
      dose), followed (if necessary) by 975 mg tid and 650 mg tid. Patient intra-escalation is not
      allowed.

      Phase II: This is a double blind, randomized, placebo-controlled Phase II multicenter study
      to evaluate ABTL0812 in combination with FOLFIRINOX for first-line treatment of metastatic
      pancreatic cancer. Patients will be randomized to one of two groups: arm A) receiving
      ABTL0812 in addition to FOLFIRINOX and arm B) receiving FOLFIRINOX plus placebo.

      Arm A) ABTL0812 + FOLFIRINOX Arm B) PLACEBO + FOLFIRINOX
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double blind, randomized, placebo-controlled, multicenter study
primary purpose: Treatment
masking: Single (Care Provider)
measure: Phase I - RP2D
time frame: 5 weeks
description: Recommended Phase II Dose (RP2D) of ABTL0812 in combination with FOLFIRINOX
measure: Phase II - PFS
time frame: 1 year
description: PFS using RECIST v1.1 by central review
measure: PFS
time frame: 1 year
description: PFS using RECIST v1.1 by investigator analysis
measure: ORR
time frame: 1 year
description: Objective response rate
measure: PFS 6 m
time frame: 6 months
description: PFS
measure: TTR
time frame: 1 year
description: Time to response
measure: DOR
time frame: 1 year
description: Duration of response
measure: OS
time frame: 5 years
description: Overall survival
measure: OS 1y
time frame: 1 year
description: Overall survival
measure: Adverse events
time frame: 1 year
description: Number of participants with Adverse Events (AE). AEs classified according to CTCAE v5.0
measure: PK - Cmax
time frame: 1 month
description: Determination of peak plasma concentration
measure: PK - AUC
time frame: 1 month
description: Determinatoin of Area under the plasma concentration versus time curve
measure: Quality of Life Questionnaire QLC-C30
time frame: 1 year
description: Quality of life measured with questionnaires QLC-C30
measure: Quality of Life Questionnaire QLQ-PAN26
time frame: 1 year
description: Quality of life measured with questionnaires QLQ-PAN26
arm group label: Arm A) ABTL0812 + FOLFIRINOX
arm group type: Experimental
description: FOLFIRINOX will be dosed according to the standard following regimen:
oxaliplatin 85 mg/m2, administered as 2-hour iv infusion
leucovorin 400 mg/m2, administered as 2-hour iv infusion
irinotecan 180 mg/m2, administered as 1.5-hour iv infusion
fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities.
ABTL0812 will be administered daily at its RP2D. ABTL0812 will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, ABTL0812 will be maintained once chemotherapy is discontinued, if ABTL0812 is tolerated and if the patient is in response or stable disease.
arm group label: Arm B) PLACEBO + FOLFIRINOX
arm group type: Experimental
description: FOLFIRINOX will be dosed according to the standard following regimen:
oxaliplatin 85 mg/m2, administered as 2-hour iv infusion
leucovorin 400 mg/m2, administered as 2-hour iv infusion
irinotecan 180 mg/m2, administered as 1.5-hour iv infusion
fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities.
Placebo will be administered at the same volume than ABTL0812 in arm A) FOLFIRINOX, then daily during chemotherapy cycles. Also, placebo will be maintained once chemotherapy is discontinued.
intervention type: Drug
intervention name: ABTL0812
description: ABTL0812 will be administered daily at its RP2D. ABTL0812 will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, ABTL0812 will be maintained once chemotherapy is discontinued, if ABTL0812 is tolerated and if the patient is in response or stable disease.
arm group label: Arm A) ABTL0812 + FOLFIRINOX
arm group label: Arm B) PLACEBO + FOLFIRINOX
intervention type: Drug
intervention name: Folfirinox
description: FOLFIRINOX will be dosed according to the standard following regimen:
oxaliplatin 85 mg/m2, administered as 2-hour iv infusion
leucovorin 400 mg/m2, administered as 2-hour iv infusion
irinotecan 180 mg/m2, administered as 1.5-hour iv infusion
fluorouracil 2400 mg/m2, administered as 46-hour iv infusionevery 2 weeks (=1 cycle) until disease progression or unacceptable toxicities.
arm group label: Arm A) ABTL0812 + FOLFIRINOX
other name: Chemotherapy
intervention type: Drug
intervention name: Placebo
description: Placebo will be administered daily at the same regim as ABTL0812. Placebo will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, placebo will be maintained once chemotherapy is discontinued, if the patient is in response or stable disease.
arm group label: Arm B) PLACEBO + FOLFIRINOX
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Cortal
role: Study Director
affiliation: Ability Pharmaceuticals SL
last name: Marc Cortal
phone: +34603141706
email: contact@abilitypharma.com
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: France
country: Israel
country: Spain
country: United States
citation: Erazo T, Lorente M, Lopez-Plana A, Munoz-Guardiola P, Fernandez-Nogueira P, Garcia-Martinez JA, Bragado P, Fuster G, Salazar M, Espadaler J, Hernandez-Losa J, Bayascas JR, Cortal M, Vidal L, Gascon P, Gomez-Ferreria M, Alfon J, Velasco G, Domenech C, Lizcano JM. The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase. Clin Cancer Res. 2016 May 15;22(10):2508-19. doi: 10.1158/1078-0432.CCR-15-1808. Epub 2015 Dec 15.
PMID: 26671995
citation: Munoz-Guardiola P, Casas J, Megias-Roda E, Sole S, Perez-Montoyo H, Yeste-Velasco M, Erazo T, Dieguez-Martinez N, Espinosa-Gil S, Munoz-Pinedo C, Yoldi G, Abad JL, Segura MF, Moran T, Romeo M, Bosch-Barrera J, Oaknin A, Alfon J, Domenech C, Fabrias G, Velasco G, Lizcano JM. The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells. Autophagy. 2021 Jun;17(6):1349-1366. doi: 10.1080/15548627.2020.1761651. Epub 2020 May 25.
PMID: 32397857
citation: Felip I, Moiola CP, Megino-Luque C, Lopez-Gil C, Cabrera S, Sole-Sanchez S, Munoz-Guardiola P, Megias-Roda E, Perez-Montoyo H, Alfon J, Yeste-Velasco M, Santacana M, Dolcet X, Reques A, Oaknin A, Rodriguez-Freixinos V, Lizcano JM, Domenech C, Gil-Moreno A, Matias-Guiu X, Colas E, Eritja N. Therapeutic potential of the new TRIB3-mediated cell autophagy anticancer drug ABTL0812 in endometrial cancer. Gynecol Oncol. 2019 May;153(2):425-435. doi: 10.1016/j.ygyno.2019.03.002. Epub 2019 Mar 7.
PMID: 30853360
citation: Lopez-Plana A, Fernandez-Nogueira P, Munoz-Guardiola P, Sole-Sanchez S, Megias-Roda E, Perez-Montoyo H, Jauregui P, Yeste-Velasco M, Gomez-Ferreria M, Erazo T, Ametller E, Recalde-Percaz L, Moragas-Garcia N, Noguera-Castells A, Mancino M, Moran T, Nadal E, Alfon J, Domenech C, Gascon P, Lizcano JM, Fuster G, Bragado P. The novel proautophagy anticancer drug ABTL0812 potentiates chemotherapy in adenocarcinoma and squamous nonsmall cell lung cancer. Int J Cancer. 2020 Aug 15;147(4):1163-1179. doi: 10.1002/ijc.32865. Epub 2020 Feb 6.
PMID: 31943158
citation: Vidal L, Victoria I, Gaba L, Martin MG, Brunet M, Colom H, Cortal M, Gomez-Ferreria M, Yeste-Velasco M, Perez A, Rodon J, Sohal DPS, Lizcano JM, Domenech C, Alfon J, Gascon P. A first-in-human phase I/Ib dose-escalation clinical trial of the autophagy inducer ABTL0812 in patients with advanced solid tumours. Eur J Cancer. 2021 Mar;146:87-94. doi: 10.1016/j.ejca.2020.12.019. Epub 2021 Feb 12.
PMID: 33588149
citation: Paris-Coderch L, Soriano A, Jimenez C, Erazo T, Munoz-Guardiola P, Masanas M, Antonelli R, Boloix A, Alfon J, Perez-Montoyo H, Yeste-Velasco M, Domenech C, Roma J, Sanchez de Toledo J, Moreno L, Lizcano JM, Gallego S, Segura MF. The antitumour drug ABTL0812 impairs neuroblastoma growth through endoplasmic reticulum stress-mediated autophagy and apoptosis. Cell Death Dis. 2020 Sep 17;11(9):773. doi: 10.1038/s41419-020-02986-w.
PMID: 32943619
citation: Mancini A, Colapietro A, Cristiano L, Rossetti A, Mattei V, Gravina GL, Perez-Montoyo H, Yeste-Velasco M, Alfon J, Domenech C, Festuccia C. Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models. Front Oncol. 2022 Nov 2;12:943064. doi: 10.3389/fonc.2022.943064. eCollection 2022.
PMID: 36408162
responsible party type: Sponsor
mesh term: Folfirinox
sharing ipd: No