<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/NCT03230318</url>
  </required_header>
  <id_info>
    <org_study_id>DZB-CS-301</org_study_id>
    <secondary_id>ARQ 087-301</secondary_id>
    <nct_id>NCT03230318</nct_id>
  </id_info>
  <brief_title>Derazantinib in Subjects With FGFR2 Gene Fusion-, Mutation- or Amplification- Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma</brief_title>
  <acronym>FIDES-01</acronym>
  <official_title>A Pivotal Study of Derazantinib in Patients With Inoperable or Advanced Intrahepatic Cholangiocarcinoma and FGFR2 Gene Fusions or FGFR2 Gene Mutations or Amplifications</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Basilea Pharmaceutica</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Basilea Pharmaceutica</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pivotal, open-label, single-arm study will evaluate the anti-cancer activity of&#xD;
      derazantinib by Objective Response Rate (ORR) by central radiology review as per RECIST v1.1&#xD;
      in subjects with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) whose tumors&#xD;
      harbor FGFR2 gene fusions (by FISH performed by the central laboratory) or FGFR2 gene&#xD;
      mutations or amplifications (based on NGS testing performed or commissioned by the respective&#xD;
      study center) and who received at least one prior regimen of systemic therapy. Subjects will&#xD;
      be dosed orally once per day at 300 mg of derazantinib capsules.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 10, 2017</start_date>
  <completion_date type="Actual">October 25, 2022</completion_date>
  <primary_completion_date type="Actual">October 25, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Substudy 1: Anti-cancer activity of derazantinib by Objective Response Rate (ORR)</measure>
    <time_frame>Up to approximately 32 weeks</time_frame>
    <description>ORR will be assessed by central radiology review as per RECIST version 1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Substudy 2: Anti-tumor activity of derazantinib by Progression Fress Survival at 3 months (PFS 3)</measure>
    <time_frame>3 months</time_frame>
    <description>PFS 3 will be assessed based on survival status or central radiology review (Response Evaluation Criteria in Solid Tumors, RECIST 1.1)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of derazantinib as assessed by adverse events</measure>
    <time_frame>Up to approximately 36 weeks</time_frame>
    <description>Adverse events will be graded using NCI CTCAE guidelines, version 4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-cancer activity of derazantinib by duration of response (DoR)</measure>
    <time_frame>Up to approximately 32 weeks</time_frame>
    <description>DoR will be assessed by central radiology review per RECIST version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-cancer activity of derazantinib by progression free survival (PFS)</measure>
    <time_frame>Up to approximately 32 weeks</time_frame>
    <description>PFS will be assessed by central radiology review per RECIST version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-cancer activity of derazantinib by overall survival (OS)</measure>
    <time_frame>Up to approximately 36 weeks</time_frame>
    <description>OS will be calculated from the first date of receiving study drug until death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire</measure>
    <time_frame>Up to approximately 36 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life as assessed by the EORTC QLQ-BIL21 questionnaire</measure>
    <time_frame>Up to approximately 36 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life as assessed by the EuroQol EQ-5D questionnaire</measure>
    <time_frame>Up to approximately 36 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Substudy 2: Anti-cancer activity of derazantinib by Objective Response Rate</measure>
    <time_frame>Up to approximately 32 weeks</time_frame>
    <description>ORR will be assessed by central radiology review as per RECIST version 1.1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">148</enrollment>
  <condition>Intrahepatic Cholangiocarcinoma</condition>
  <condition>Combined Hepatocellular and Cholangiocarcinoma</condition>
  <arm_group>
    <arm_group_label>derazantinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>derazantinib</intervention_name>
    <description>derazantinib will be orally administered at 300 mg once per day one hour prior to or two hours after a meal and is supplied as 100 mg capsules.</description>
    <arm_group_label>derazantinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed written informed consent granted prior to initiation of any study-specific&#xD;
             procedures&#xD;
&#xD;
          2. 18 years of age or older&#xD;
&#xD;
          3. Histologically or cytologically confirmed locally advanced, inoperable (where surgery&#xD;
             is not indicated due to disease extension, co-morbidities, or other technical&#xD;
             reasons), or metastatic iCCA or mixed histology tumors (combined&#xD;
             hepatocellular-cholangiocarcinoma [cHCC-CCA])&#xD;
&#xD;
          4. Substudy 1: FGFR2 fusion status based on the following assessments:&#xD;
&#xD;
             a) If central laboratory designated by Sponsor: Positive FISH test; and/or b) If&#xD;
             non-central laboratory: i) Positive FISH or NGS test: patients may be enrolled and may&#xD;
             start dosing, but central confirmation is required* ii) Negative FISH or NGS test:&#xD;
             tissue may be submitted to the central laboratory designated by the Sponsor, and&#xD;
             patients may only be enrolled if the central test is positive&#xD;
&#xD;
             *Using standard protocols and approved by local IRB/EC, by CLIA or other similar&#xD;
             agency.&#xD;
&#xD;
             Substudy 2: FGFR2 mutation/amplification status based on local NGS testing performed&#xD;
             or commissioned by the respective study site.&#xD;
&#xD;
          5. Received at least one regimen of prior systemic therapy and then experienced&#xD;
             documented radiographic progression&#xD;
&#xD;
          6. Measurable disease by RECIST version 1.1 criteria&#xD;
&#xD;
          7. ECOG performance status ≤ 1&#xD;
&#xD;
          8. Adequate organ functions as indicated by the following laboratory values (based on&#xD;
             screening visit values from the central laboratory).&#xD;
&#xD;
               -  Hematological&#xD;
&#xD;
                    -  Hemoglobin (Hgb) ≥ 9.0 g/dL&#xD;
&#xD;
                    -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L&#xD;
&#xD;
                    -  Platelet count ≥ 75 x 109/L&#xD;
&#xD;
                    -  International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤&#xD;
                       3 for subjects receiving anticoagulant therapy such as Coumadin or heparin&#xD;
&#xD;
               -  Hepatic&#xD;
&#xD;
                    -  Total bilirubin ≤ 2 x ULN&#xD;
&#xD;
                    -  AST and ALT ≤ 3 ULN (≤ 5 x ULN for subjects with liver metastases)&#xD;
&#xD;
                    -  Albumin ≥ 2.8 g/dL&#xD;
&#xD;
               -  Renal&#xD;
&#xD;
                    -  Serum creatinine ≤ 1.5 x ULN&#xD;
&#xD;
                    -  Creatinine clearance of ≥ 30 mL/min as estimated by the Cockcroft-Gault&#xD;
                       equation&#xD;
&#xD;
          9. Female and male patients of child-producing potential must agree to avoid becoming&#xD;
             pregnant or impregnating a partner, respectively, use double-barrier contraceptive&#xD;
             measures, oral contraception, or avoidance of intercourse, during the study*, and&#xD;
             until at least 120 for 90 days after the last dose of derazantinib.&#xD;
&#xD;
             *From the day of first study medication, or for oral contraception from 14 days before&#xD;
             first study medication.&#xD;
&#xD;
             Male patients are considered not to be of child-producing potential if they have&#xD;
             azoospermia (whether due to vasectomy or an underlying medical condition). Female&#xD;
             patients are considered not to be of child-producing potential if they are:&#xD;
&#xD;
               -  postmenopausal* , or&#xD;
&#xD;
               -  have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or&#xD;
                  bilateral tubal ligation/occlusion, at least 6 weeks prior to screening, or&#xD;
&#xD;
               -  have a congenital or acquired condition that prevents childbearing.&#xD;
&#xD;
             Male or female patients of child-producing potential must agree to comply with one of&#xD;
             the following until at least 120 days after the last dose of derazantinib:&#xD;
&#xD;
               1. Abstinence from heterosexual activity**&#xD;
&#xD;
               2. Using (or having their partner use) an acceptable method of contraception during&#xD;
                  heterosexual activity. Acceptable methods of contraception are***:&#xD;
&#xD;
                    -  any ONE of:&#xD;
&#xD;
                       - an intrauterine device (IUD)&#xD;
&#xD;
                       - vasectomy of a female patient's male partner&#xD;
&#xD;
                       - a contraceptive rod implanted into the skin.&#xD;
&#xD;
                    -  any TWO in combination of:&#xD;
&#xD;
                       - diaphragm with spermicide (cannot be used in conjunction with cervical&#xD;
                       cap/spermicide)&#xD;
&#xD;
                       - cervical cap with spermicide (nulliparous women only)&#xD;
&#xD;
                       - contraceptive sponge (nulliparous women only)&#xD;
&#xD;
                       - male condom or female condom (cannot be used together)&#xD;
&#xD;
                       - hormonal contraceptive (oral contraceptive pill [estrogen/progestin pill&#xD;
                       or progestin-only pill], contraceptive skin patch, vaginal contraceptive&#xD;
                       ring, or subcutaneous contraceptive injection)&#xD;
&#xD;
                       *Postmenopausal is defined as at least 12 months with no menses without an&#xD;
                       alternative medical cause; in women &lt; 45 years of age a high follicle&#xD;
                       stimulating hormone (FSH) level in the postmenopausal range may be used to&#xD;
                       confirm a post -menopausal state in women not using hormonal contraception&#xD;
                       or hormonal replacement therapy. In the absence of 12 months of amenorrhea,&#xD;
                       a single FSH measurement is not sufficient.&#xD;
&#xD;
                         -  Abstinence (relative to heterosexual activity) can be used as the sole&#xD;
                            method of contraception if it is consistently employed as the subject's&#xD;
                            preferred and usual lifestyle and if considered acceptable by local&#xD;
                            regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar,&#xD;
                            ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal&#xD;
                            are not acceptable methods of contraception.&#xD;
&#xD;
                              -  If a contraceptive method listed above is restricted by local&#xD;
                                 regulations/guidelines, then it does not qualify as an acceptable&#xD;
                                 method of contraception for subjects participating at sites in&#xD;
                                 this country/region.&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
          1. Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an&#xD;
             interval shorter than the following, as applicable:&#xD;
&#xD;
               -  One chemotherapy or biological (e.g., antibody) cycle interval&#xD;
&#xD;
               -  Five half-lives of any small-molecule investigational or licensed medicinal&#xD;
                  product&#xD;
&#xD;
               -  Two weeks, for any investigational medicinal product with an unknown half-life&#xD;
&#xD;
               -  Four weeks of curative radiotherapy&#xD;
&#xD;
               -  Seven days of palliative radiotherapy&#xD;
&#xD;
               -  28 days of radiotherapy&#xD;
&#xD;
          2. Major surgery, locoregional therapy, or radiation therapy within four weeks of the&#xD;
             first dose of derazantinib&#xD;
&#xD;
          3. Previous treatment with any FGFR inhibitor (e.g., Balversa® [erdafitinib], Pemazyre®&#xD;
             [pemigatinib], infigratinib, rogaratinib, futibatinib, lenvatinib, ponatinib,&#xD;
             dovitinib, nintedanib, AZD4547, LY2784455).&#xD;
&#xD;
             - Subjects who received less than four weeks of therapy and were unable to continue&#xD;
             therapy due to toxicity will be allowed to participate&#xD;
&#xD;
          4. Unable or unwilling to swallow the complete daily dose of derazantinib capsules&#xD;
&#xD;
          5. Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects&#xD;
             must have stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or&#xD;
             computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose&#xD;
             steroids, anti-epileptics, or other symptom-relieving medications)&#xD;
&#xD;
          6. Current evidence of clinically significant corneal or retinal disorder likely to&#xD;
             increase the risk of eye toxicity, including but not limited to bullous/band&#xD;
             keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal&#xD;
             abrasion, inflammation/ulceration, confirmed by ophthalmologic examination.&#xD;
&#xD;
          7. Concurrent uncontrolled or active hepatobiliary disorders, untreated or ongoing&#xD;
             complications after laparoscopic procedures or stent placement, including but not&#xD;
             limited to active cholangitis, biloma or abscess (to be eligible, the subjects have to&#xD;
             be treated and disorders/complications should be resolved within 2 weeks prior to the&#xD;
             first dose of derazantinib)&#xD;
&#xD;
          8. History of significant cardiac disorders:&#xD;
&#xD;
               -  Myocardial infarction (MI) or congestive heart failure defined as Class II to IV&#xD;
                  per the New York Heart Association (NYHA) classification within 6 months of the&#xD;
                  first dose of derazantinib (MI that occurred &gt; 6 months prior to the first dose&#xD;
                  of derazantinib will be permitted)&#xD;
&#xD;
               -  QTcF &gt;450 msec (males or females)&#xD;
&#xD;
          9. Serum electrolyte abnormalities defined as follows:&#xD;
&#xD;
             - Hyperphosphataemia: Serum phosphate &gt; institutional ULN&#xD;
&#xD;
             - Hyperkalemia: &gt; 6.0 mmol/L&#xD;
&#xD;
             - Hypokalemia: &lt; 3.0 mmol/L&#xD;
&#xD;
             - Hypercalcemia: corrected serum calcium &lt; 1.75 mmol/L (&lt; 7.0 mg/dL)&#xD;
&#xD;
               -  Hypocalcemia: corrected serum calcium &gt; 3.1 mmol/L (&gt; 12.5 mg/dL)&#xD;
&#xD;
               -  Hypomagnesemia: &lt; 0.4 mmol/L (&lt; 0.9 mg/dL)&#xD;
&#xD;
         10. Significant gastrointestinal disorder(s) that could, in the opinion of the&#xD;
             Investigator, interfere with the absorption, metabolism, or excretion of derazantinib&#xD;
             (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)&#xD;
&#xD;
         11. History of additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy, and in situ cervical cancer.&#xD;
&#xD;
         12. Concurrent uncontrolled illness not related to cancer, including but not limited to:&#xD;
&#xD;
               -  Psychiatric illness/substance abuse/social situation that would limit compliance&#xD;
                  with study requirements&#xD;
&#xD;
               -  Known uncontrolled human immunodeficiency virus (HIV) infection&#xD;
&#xD;
               -  Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral&#xD;
                  or IV medication at the time of first dose of study drug administration&#xD;
&#xD;
         13. Blood or albumin transfusion within 5 days of the blood draw being used to confirm&#xD;
             eligibility&#xD;
&#xD;
         14. Pregnant or breast feeding&#xD;
&#xD;
         15. Known hypsersensitivity to derazantinib, or to any of the study drug excipients&#xD;
             (starch, lactose, crospovidone, magnesium stearate)&#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 Engelhardt, MD</last_name>
    <role>Study Director</role>
    <affiliation>Basilea Pharmaceutica International Ltd</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612-9416</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute of Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center - Sidney Kimmel Center for Prostate and Urologic Cancers</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065-6800</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abramson Cancer Center of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt-Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Erasme</name>
      <address>
        <city>Brussels</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antwerp University Hospital</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tom Baker Cancer Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Grenoble Alpes</name>
      <address>
        <city>La Tronche</city>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Frankfurt</name>
      <address>
        <city>Frankfurt am Main</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Hamburg-Eppendorf (UKE)</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover (MHH)</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum des Saarlandes</name>
      <address>
        <city>Homburg</city>
        <zip>66421</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin der Johannes Gutenberg-Universität Mainz</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. James's Hospital</name>
      <address>
        <city>Dublin</city>
        <zip>D08 NHY1</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sant'Orsola-Malpighi Hospital, University of Bologna</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Gerardo</name>
      <address>
        <city>Monza</city>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Oncologico Veneto - IRCCS</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS</name>
      <address>
        <city>Rozzano</city>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>3080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>6351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea, Seoul St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>6591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vall d'Hebrón University Hospital</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catalan Institute of Oncology</name>
      <address>
        <city>Barcelona</city>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsspital Basel</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals NHS Foundation Trust</name>
      <address>
        <city>Euston</city>
        <zip>NW1 2BU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Centre</name>
      <address>
        <city>Glasgow</city>
        <zip>G120YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden</name>
      <address>
        <city>Sutton</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>iCCA</keyword>
  <keyword>intrahepatic cholangiocarcinoma</keyword>
  <keyword>FGFR2 gene fusion or FGFR2 gene mutation or amplification</keyword>
  <keyword>biliary cancer</keyword>
  <keyword>bile duct cancer</keyword>
  <keyword>FGFR2 gene rearrangement</keyword>
  <keyword>liver cancer</keyword>
  <keyword>targeted therapy</keyword>
  <keyword>combined hepatocellular and cholangiocarcinoma</keyword>
  <keyword>cHCC-CCA</keyword>
  <keyword>derazantinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholangiocarcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_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/NCT03230318
org study id: DZB-CS-301
secondary id: ARQ 087-301
nct id: NCT03230318
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This pivotal, open-label, single-arm study will evaluate the anti-cancer activity of
      derazantinib by Objective Response Rate (ORR) by central radiology review as per RECIST v1.1
      in subjects with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) whose tumors
      harbor FGFR2 gene fusions (by FISH performed by the central laboratory) or FGFR2 gene
      mutations or amplifications (based on NGS testing performed or commissioned by the respective
      study center) and who received at least one prior regimen of systemic therapy. Subjects will
      be dosed orally once per day at 300 mg of derazantinib capsules.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Substudy 1: Anti-cancer activity of derazantinib by Objective Response Rate (ORR)
time frame: Up to approximately 32 weeks
description: ORR will be assessed by central radiology review as per RECIST version 1.1
measure: Substudy 2: Anti-tumor activity of derazantinib by Progression Fress Survival at 3 months (PFS 3)
time frame: 3 months
description: PFS 3 will be assessed based on survival status or central radiology review (Response Evaluation Criteria in Solid Tumors, RECIST 1.1)
measure: Safety of derazantinib as assessed by adverse events
time frame: Up to approximately 36 weeks
description: Adverse events will be graded using NCI CTCAE guidelines, version 4.03
measure: Anti-cancer activity of derazantinib by duration of response (DoR)
time frame: Up to approximately 32 weeks
description: DoR will be assessed by central radiology review per RECIST version 1.1
measure: Anti-cancer activity of derazantinib by progression free survival (PFS)
time frame: Up to approximately 32 weeks
description: PFS will be assessed by central radiology review per RECIST version 1.1
measure: Anti-cancer activity of derazantinib by overall survival (OS)
time frame: Up to approximately 36 weeks
description: OS will be calculated from the first date of receiving study drug until death
measure: Health-related quality of life as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire
time frame: Up to approximately 36 weeks
measure: Health-related quality of life as assessed by the EORTC QLQ-BIL21 questionnaire
time frame: Up to approximately 36 weeks
measure: Health-related quality of life as assessed by the EuroQol EQ-5D questionnaire
time frame: Up to approximately 36 weeks
measure: Substudy 2: Anti-cancer activity of derazantinib by Objective Response Rate
time frame: Up to approximately 32 weeks
description: ORR will be assessed by central radiology review as per RECIST version 1.1
arm group label: derazantinib
arm group type: Experimental
description: Oral administration
intervention type: Drug
intervention name: derazantinib
description: derazantinib will be orally administered at 300 mg once per day one hour prior to or two hours after a meal and is supplied as 100 mg capsules.
arm group label: derazantinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Engelhardt, MD
role: Study Director
affiliation: Basilea Pharmaceutica International Ltd
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country: Belgium
country: Canada
country: France
country: Germany
country: Ireland
country: Italy
country: Korea, Republic of
country: Spain
country: Switzerland
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Cholangiocarcinoma
mesh term: Carcinoma, Hepatocellular
sharing ipd: No