xml: <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/NCT06037980</url>
    </required_header>
    <id_info>
      <org_study_id>PURITY</org_study_id>
      <nct_id>NCT06037980</nct_id>
    </id_info>
    <brief_title>CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence</brief_title>
    <acronym>PURITY</acronym>
    <official_title>A Phase II/III Randomized Clinical Trial of CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence: PURITY Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Gruppo Oncologico del Nord-Ovest</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Gruppo Oncologico del Nord-Ovest</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        PURITY is a multicentre, randomized adaptive phase II/III trial aimed at comparing the&#xD;
        triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment (ARM&#xD;
        A) versus standard upfront surgery (ARM B) in terms of 12-month PFS rate (phase II part) and&#xD;
        PFS (phase III part) in patients with resectable BTC at high risk for recurrence.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PURITY is a multicentre, randomized adaptive phase II/III trial aimed at comparing the&#xD;
        triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment (ARM&#xD;
        A) versus standard upfront surgery (ARM B) in terms of 12-month PFS rate (phase II part) and&#xD;
        PFS (phase III part) in patients with resectable BTC at high risk for recurrence.&#xD;
  &#xD;
        High risk for recurrence, for which patients will be eligible for study, is defined by the&#xD;
        presence of at least one of the following risk features, as evaluated at baseline&#xD;
        (pre-surgery):&#xD;
  &#xD;
          1. For cholangiocarcinoma:&#xD;
  &#xD;
               -  Suspected or definite locoregional lymph node involvement in the absence of&#xD;
                  jaundice (at least one of the following):&#xD;
  &#xD;
                    -  positive FNA cytology (obtained by EUS).&#xD;
  &#xD;
                    -  positive locoregional lymph nodes at PET-CT.&#xD;
  &#xD;
                    -  suspected positive locoregional lymph nodes at imaging (CT or MRI scan)&#xD;
                       according to local MTD discussion (eg. short axis &gt; 1.5 cm, contrast&#xD;
                       enhancement uptake, round shape, restriction at DWI).&#xD;
  &#xD;
               -  Macrovascular invasion at preoperative CT scan.&#xD;
  &#xD;
               -  Expected R1 resection due to proximity to major intrahepatic vascular and biliary&#xD;
                  structures.&#xD;
  &#xD;
               -  For iCCA, presence of satellitosis or multifocal disease or radiological suspicion&#xD;
                  of tumoral diaphragmatic adhesion.&#xD;
  &#xD;
               -  For iCCA, size of the liver lesion &gt;5 cm.&#xD;
  &#xD;
               -  For eCCA, size of the primary lesion &gt; 3cm.&#xD;
  &#xD;
               -  Ca19.9 &gt;100 U/mL.&#xD;
  &#xD;
          2. For GBC:&#xD;
  &#xD;
               -  Incidentally Detected Gallbladder Carcinoma (IGBC) After Simple Cholecystectomy&#xD;
                  with indication for radical second surgery (&gt;pT2) or newly diagnosed GBC.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">January 2029</completion_date>
    <primary_completion_date type="Anticipated">December 2028</primary_completion_date>
    <phase>Phase 2/Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Prospective, open-label, multicenter, randomized phase II-III study</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>12-month progression-free survival (PFS) rate</measure>
      <time_frame>12 months</time_frame>
      <description>the proportion of patients alive and free from progression/post-resection recurrence by 12-months timepoint from randomization (to be considered as primary endpoint in the phase II part of the study and as secondary endpoint in the phase III part of the study).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>median PFS</measure>
      <time_frame>From date of randomization until the date of first documented progression (as assessed by radiological evaluation and clinical examination) or date of death from any cause, whichever came first, assessed up to 120 months</time_frame>
      <description>i.e. the time from randomization to disease progression, post-resection recurrence or death from any cause (to be considered as secondary endpoint in the phase II part of the study and as primary endpoint in the phase III part of the study).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Median event free survival</measure>
      <time_frame>from date of randomization to date of disease progression that precludes definitive surgery, of treatment discontinuation for any reason, of post-resection recurrence, of diagnosis of a second primary cancer, or of death from any cause</time_frame>
      <description>i.e. the time from randomization to disease progression that precludes definitive surgery, treatment discontinuation for any reason, post-resection recurrence, a second primary cancer, or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median relapse free survival</measure>
      <time_frame>from date of surgery to date of disease recurrence or date of death, whichever came first, in patients who undergo surgery with curative intent, assessed up to 120 months.</time_frame>
      <description>i.e. the time from surgery to disease recurrence or death in patients who undergo to surgery with curative intent.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Overall survival</measure>
      <time_frame>from date of randomization to date of death (or last follow up for alive patients), assessed up to 120 months.</time_frame>
      <description>i.e. the time from randomization to death or last follow-up for alive patients.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>R0 resection rate</measure>
      <time_frame>At surgery</time_frame>
      <description>i.e. the percentage of patients, relative to the total of randomized patients, for whom a R0 resection is achieved.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>R0+R1 resection rate</measure>
      <time_frame>At surgery</time_frame>
      <description>i.e. the percentage of patients, relative to the total of randomized patients, for whom the tumor was macroscopically removed and the intent of surgery is considered curative.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life EORTC QLQ-C30 scores</measure>
      <time_frame>Quality of life questionnaires will be compiled during screening (28 days before randomisation) and at restaging before (week 8 to 10 after randomisation) and after surgery (week 6 to 16 after surgery)</time_frame>
      <description>QoL will be estimated with EORTC QLQ-C30; mean score changes from baseline, proportion of patients with improved, stable, or deteriorated scores from baseline and time to deterioration in the EORTC QLQ-C30 scores will be compared between the two arms. Time to deterioration will be defined as the time from baseline to the first onset of a 10-point or greater decrease (for functional scales)/increase (for symptoms scale) from baseline, with confirmation under the right-censoring rule. All available observations will be used to calculate time to deterioration.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life BIL21 scores</measure>
      <time_frame>Quality of life questionnaires will be compiled during screening (28 days before randomisation) and at restaging before (week 8 to 10 after randomisation) and after surgery (week 6 to 16 after surgery)</time_frame>
      <description>QoL will be estimated with the module BIL21; mean score changes from baseline, proportion of patients with improved, stable, or deteriorated scores from baseline and time to deterioration in the BIL21 physical functioning, social functioning, and fatigue scores will be compared between the two arms. Time to deterioration was defined as the time from baseline to the first onset of a 10-point or greater decrease from baseline for functional scales or a 10-point or greater increase for symptom scales, with confirmation under the right-censoring rule. All available observations will be used to calculate time to deterioration.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall response rate</measure>
      <time_frame>At radiological evaluation as performed at restaging before surgery (week 8 to 10 after randomisation)</time_frame>
      <description>of neoadjuvant therapy as per investigator assessment and central review, i.e. the percentage of patients, relative to the total of enrolled subjects receiving neoadjuvant treatment, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Resectability rate of primary tumor</measure>
      <time_frame>Resectability rate will be assessed before surgery (after the 3 cycles of neoadjuvant chemotherapy for the experimental treatment arm)</time_frame>
      <description>i.e. the retrospective evaluation of patients with unresectable disease, as assessed by the central review committee, in the two arms, and of the rate of conversion to resectability in the neoadjuvant arm.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Toxicity rates</measure>
      <time_frame>Through study completion, an average of 1 year for each patient</time_frame>
      <description>.e. the percentage of patients, relative to the total of subjects randomized to neoadjuvant treatment, experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Perioperative morbidity and mortality</measure>
      <time_frame>At surgery</time_frame>
      <description>i.e. the percentage of patients, relative to the total of enrolled subjects undergoing surgery, with any serious perioperative morbidity or mortality according to Clavien-Dindo classification.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">300</enrollment>
    <condition>Biliary Tract Cancer</condition>
    <condition>Cholangiocarcinoma</condition>
    <arm_group>
      <arm_group_label>Preoperative chemotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment followed by surgery and adjuvant chemotherapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Upfront surgery</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Standard upfront surgery and adjuvant chemotherapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Gemcitabine</intervention_name>
      <description>◦ Gemcitabine 800 mg/mq iv, day 1 and 8 of 21-day cycles, for 3 cycles</description>
      <arm_group_label>Preoperative chemotherapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nab paclitaxel</intervention_name>
      <description>◦ Nab-paclitaxel 100 mg/mq, day 1 and 8 of 21-day cycles, for 3 cycles</description>
      <arm_group_label>Preoperative chemotherapy</arm_group_label>
      <other_name>Abraxane</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cisplatin</intervention_name>
      <description>◦ Cisplatin 25 mg/mq iv, day 1 and 8 of 21-day cycles, for 3 cycles</description>
      <arm_group_label>Preoperative chemotherapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Curative Surgery</intervention_name>
      <description>Curative surgery on primary tumor</description>
      <arm_group_label>Preoperative chemotherapy</arm_group_label>
      <arm_group_label>Upfront surgery</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Capecitabine</intervention_name>
      <description>1250 mg/m2 given orally twice daily on days 1 to 14 of a 3 weekly cycle for a total of 8 cycles</description>
      <arm_group_label>Preoperative chemotherapy</arm_group_label>
      <arm_group_label>Upfront surgery</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patient able and willing to provide written informed consent and to comply with the&#xD;
               study protocol and with the planned surgical procedures.&#xD;
  &#xD;
            2. Female and male patients ≥18 years and &lt;75 years.&#xD;
  &#xD;
            3. Histologically or cytologically confirmed non metastatic resectable carcinoma of&#xD;
               biliary tract (BTC), including gallbladder carcinoma (GBC), intrahepatic,&#xD;
               periperihilar or distal Cholangiocarcinoma (CCA). Mixed tumor entities with&#xD;
               hepatocellular carcinoma and ampullary cancers are excluded.&#xD;
  &#xD;
            4. Availability of a tumoral sample&#xD;
  &#xD;
            5. ECOG performance status of 0-1.&#xD;
  &#xD;
            6. No prior tumor resection for BTC.&#xD;
  &#xD;
            7. Exclusion of distant metastases by CT or MRI of abdomen, pelvis, and thorax and PET&#xD;
               scan.&#xD;
  &#xD;
            8. Technically resectable BTC as per local Multidisciplinary Team (MDT) assessment,&#xD;
               including a core team with at least one medical oncologist, one surgeon, one&#xD;
               radiologist, one endoscopist/gastroenterologist and one pathologist, all with&#xD;
               expertise &gt; 3 years on biliary tract cancer and hepatobiliary oncology.&#xD;
  &#xD;
            9. High risk for recurrence defined as the presence of at least one of the following risk&#xD;
               features, as evaluated at baseline (pre-surgery):&#xD;
  &#xD;
                 1. For cholangiocarcinoma:&#xD;
  &#xD;
                      -  Suspected or definite locoregional lymph node involvement (at least one of&#xD;
                         the following):&#xD;
  &#xD;
                           -  positive FNA cytology (obtained by EUS).&#xD;
  &#xD;
                           -  positive locoregional lymph nodes at PET-CT.&#xD;
  &#xD;
                           -  suspected positive locoregional lymph nodes at imaging (CT or MRI scan)&#xD;
                              according to local MDT discussion (eg. short axis &gt; 1.5 cm, contrast&#xD;
                              enhancement uptake, round shape, restriction at DWI).&#xD;
  &#xD;
                      -  Macrovascular invasion at preoperative CT scan.&#xD;
  &#xD;
                      -  Expected R1 resection due to proximity to major intrahepatic vascular and&#xD;
                         biliary structures.&#xD;
  &#xD;
                      -  For iCCA, presence of satellitosis or multifocal disease or radiological&#xD;
                         suspicion of tumoral diaphragmatic adhesion.&#xD;
  &#xD;
                      -  For iCCA, size of the liver lesion &gt;5 cm.&#xD;
  &#xD;
                      -  For eCCA, size of the primary lesion &gt; 3cm.&#xD;
  &#xD;
                      -  Ca19.9 &gt;100 U/mL.&#xD;
  &#xD;
                 2. For GBC:&#xD;
  &#xD;
                      -  Incidentally Detected Gallbladder Carcinoma (IGBC) after simple&#xD;
                         cholecystectomy with indication for radical second surgery (&gt;pT2) or newly&#xD;
                         diagnosed GBC.&#xD;
  &#xD;
           10. Estimated life expectancy &gt; 3 months.&#xD;
  &#xD;
           11. Adequate baseline hematologic function characterized by the following at screening:&#xD;
  &#xD;
                 1. ANC ≥ 1.5 × 109/L&#xD;
  &#xD;
                 2. platelets ≥ 100 × 109/L&#xD;
  &#xD;
                 3. hemoglobin ≥ 9 g/dl. Note: prior transfusions for patients with low hemoglobin&#xD;
                    are allowed.&#xD;
  &#xD;
           12. Adequate liver function characterized by the following at screening:&#xD;
  &#xD;
                 1. Serum total bilirubin ≤ 1.5 × ULN and &lt; 2 mg/dL. Note: Subjects with Serum total&#xD;
                    bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or &lt; 40% of total bilirubin&#xD;
                    are allowed.&#xD;
  &#xD;
                 2. Serum transaminases (AST and/or ALT) &lt; 3 x ULN.&#xD;
  &#xD;
           13. Adequate renal function, i.e. serum creatinine ≤ 1.5 x institutional ULN and&#xD;
               calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50&#xD;
               mL/min&#xD;
  &#xD;
           14. Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤&#xD;
               1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless&#xD;
               receiving anticoagulation therapy).&#xD;
  &#xD;
           15. No presence of complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency with&#xD;
               DPYD gene testing mandatory at screening as per national guidelines&#xD;
  &#xD;
           16. Females of childbearing potential must agree to remain abstinent (refrain from sexual&#xD;
               intercourse) or use highly effective contraceptive methods, as defined in APPENDIX V&#xD;
               of the full protocol, during the treatment period and for at least 7 months after the&#xD;
               last administration of study treatments.&#xD;
  &#xD;
           17. Males must agree to remain abstinent (refrain from sexual intercourse) or use highly&#xD;
               effective contraceptive methods, as defined in APPENDIX V of the full protocol.&#xD;
  &#xD;
           18. Negative serum pregnancy test within 7 days of starting study treatment in&#xD;
               pre-menopausal women and women &lt;1 year after the onset of menopause.&#xD;
  &#xD;
           19. A participant must agree not to donate eggs/sperm for future use for the purposes of&#xD;
               assisted reproduction during the study and for a period of 7 months after receiving&#xD;
               the last dose of study treatment. Female and male participants should consider&#xD;
               preservation of eggs/sperm prior to study treatment as anti-cancer treatments may&#xD;
               impair fertility.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Known allergy or hypersensitivity to any of the study drugs.&#xD;
  &#xD;
            2. Any known additional malignancy that is progressing or requires active treatment, or&#xD;
               history of other malignancy within 2 years of study entry except for curatively&#xD;
               treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and&#xD;
               prostate cancer.&#xD;
  &#xD;
            3. Locally unresectable tumor according to local MDT (including radiological evidence&#xD;
               suggesting inability to resect with curative intent whilst maintaining adequate&#xD;
               vascular inflow and outflow, and sufficient future liver remnant).&#xD;
  &#xD;
            4. Evidence of distant metastases at any site.&#xD;
  &#xD;
            5. Tumors requiring multi-step surgical procedures such as two-stage hepatectomy or&#xD;
               Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS)&#xD;
               due to liver volumetry-based assessment of anticipated inadequate future liver&#xD;
               remnant.&#xD;
  &#xD;
            6. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a&#xD;
               history of hepatic decompensation in the year before enrolment.&#xD;
  &#xD;
            7. Know active uncontrolled hepatitis B or hepatitis C. Patients with a past or resolved&#xD;
               HBV infection are eligible. Patients with chronic disease controlled by antiviral&#xD;
               therapy or requiring prophylactic treatment are eligible.&#xD;
  &#xD;
            8. Chronic or current active infectious disease requiring systemic antibiotics or&#xD;
               antifungal treatment within 2 weeks prior to enrollment.&#xD;
  &#xD;
            9. Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+&#xD;
               cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable&#xD;
               per standard of care assay, and they must be compliant with antiretroviral treatment.&#xD;
  &#xD;
           10. Pregnant or breast-feeding patient, or patient is planning to become pregnant within 7&#xD;
               months after the end of treatment.&#xD;
  &#xD;
           11. Any other concurrent antineoplastic treatment including radiotherapy.&#xD;
  &#xD;
           12. Previous or concurrent systemic (eg cytotoxic or targeted or other experimental drugs)&#xD;
               therapy for BTC.&#xD;
  &#xD;
           13. Prior surgery or locoregional therapy for BTC.&#xD;
  &#xD;
           14. Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or&#xD;
               IV, unstable angina pectoris, history of myocardial infarction in the last three&#xD;
               months, significant arrhythmia).&#xD;
  &#xD;
           15. Presence of psychiatric disorder precluding understanding of information of trial&#xD;
               related topics and giving informed consent.&#xD;
  &#xD;
           16. Any serious underlying medical conditions (judged by the investigator), that could&#xD;
               impair the ability of the patient to participate in the trial.&#xD;
  &#xD;
           17. Presence of complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency with DPYD&#xD;
               gene testing mandatory at screening as per national guidelines.&#xD;
  &#xD;
           18. Lack of physical integrity of the upper gastrointestinal tract, malabsorption&#xD;
               syndrome, or inability to take oral medication.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Monica Niger, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori di Milano</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Monica Niger, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>02 2390 2919</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Monica Niger, MD</last_name>
      <phone>02 2390 2919</phone>
      <email>monica.niger@istitutotumori.mi.it</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Federico Nichetti, MD</last_name>
      <phone>02 2390 3586</phone>
      <email>PURITYstudy@istitutotumori.mi.it</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Ospedali Riuniti di Ancona</name>
        <address>
          <city>Ancona</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Rossana Berardi</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>ASST Papa Giovanni XXIII</name>
        <address>
          <city>Bergamo</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Stefania Mosconi</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Oncologia Medica Policlinico Sant'Orsola - Malpighi</name>
        <address>
          <city>Bologna</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Giovanni Brandi</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>ASST Spedali Civili</name>
        <address>
          <city>Brescia</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Giuseppina Arcangeli</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Azienda Ospedaliera S. Croce e Carle</name>
        <address>
          <city>Cuneo</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Elena Fea</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>IRST Dino Amadori</name>
        <address>
          <city>Meldola</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Ilario Giovanni Rapposelli</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Ospedale San Raffaele</name>
        <address>
          <city>Milano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrea Casadei Gardini</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
        <address>
          <city>Milan</city>
          <zip>20133</zip>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Federico Nichetti</last_name>
        <phone>02 2390 3586</phone>
        <email>PURITYstudy@istitutotumori.mi.it</email>
      </contact>
      <contact_backup>
        <last_name>Federica Palermo</last_name>
        <phone>02 2390 3835</phone>
        <email>federica.palermo@istitutotumori.mi.it</email>
      </contact_backup>
      <investigator>
        <last_name>Federico Nichetti, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Monica Niger, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Humanitas Cancer Center</name>
        <address>
          <city>Milan</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Lorenza Rimassa</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Ospedale Niguarda Cancer Center</name>
        <address>
          <city>Milan</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Salvatore Siena</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Università di Modena</name>
        <address>
          <city>Modena</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Massimilano Salati</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Ospedale S. Gerardo</name>
        <address>
          <city>Monza</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Raffaella Longarini</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>IOV</name>
        <address>
          <city>Padova</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Francesca Bergamo</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Policlinico San Matteo</name>
        <address>
          <city>Pavia</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Salvatore Corallo</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Azienda Ospedaliera Universitaria Pisa</name>
        <address>
          <city>Pisa</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Lorenzo Fornaro</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>IRST (Cesena-Forlì-Meldola)</name>
        <address>
          <city>Ravenna</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Stefano Tamberi</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Policlinico Gemelli</name>
        <address>
          <city>Rome</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Lisa Salvatore</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Azienda Ospedaliera Ordine Mauriziano</name>
        <address>
          <city>Turin</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Massimo Di Maio</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>AOUI Verona - Policlinico &quot;G.B. Rossi&quot;</name>
        <address>
          <city>Verona</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Davide Melisi</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <results_reference>
      <citation>Yadav S, Xie H, Bin-Riaz I, Sharma P, Durani U, Goyal G, Borah B, Borad MJ, Smoot RL, Roberts LR, Go RS, McWilliams RR, Mahipal A. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis. Eur J Surg Oncol. 2019 Aug;45(8):1432-1438. doi: 10.1016/j.ejso.2019.03.023. Epub 2019 Mar 21.</citation>
      <PMID>30914290</PMID>
    </results_reference>
    <results_reference>
      <citation>Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, Raghav KPS, Iwasaki M, Masci P, Ramanathan RK, Ahn DH, Bekaii-Saab TS, Borad MJ. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):824-830. doi: 10.1001/jamaoncol.2019.0270.</citation>
      <PMID>30998813</PMID>
    </results_reference>
    <results_reference>
      <citation>Maithel SK, Keilson JM, Cao HST, Rupji M, Mahipal A, Lin BS, Javle MM, Cleary SP, Akce M, Switchenko JM, Rocha FG. NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2023 Jun 27. doi: 10.1245/s10434-023-13809-5. Online ahead of print.</citation>
      <PMID>37368098</PMID>
    </results_reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Biliary Tract Cancers</keyword>
    <keyword>Cholangiocarcinoma</keyword>
    <keyword>Neoadjuvant Chemotherapy</keyword>
    <keyword>Cisplatin Gemcitabine Nabpaclitaxel</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cholangiocarcinoma</mesh_term>
      <mesh_term>Biliary Tract Neoplasms</mesh_term>
      <mesh_term>Recurrence</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Paclitaxel</mesh_term>
      <mesh_term>Gemcitabine</mesh_term>
      <mesh_term>Capecitabine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06037980
  org study id: PURITY
  nct id: NCT06037980
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  PURITY is a multicentre, randomized adaptive phase II/III trial aimed at comparing the
        triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment (ARM
        A) versus standard upfront surgery (ARM B) in terms of 12-month PFS rate (phase II part) and
        PFS (phase III part) in patients with resectable BTC at high risk for recurrence.
  PURITY is a multicentre, randomized adaptive phase II/III trial aimed at comparing the
        triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment (ARM
        A) versus standard upfront surgery (ARM B) in terms of 12-month PFS rate (phase II part) and
        PFS (phase III part) in patients with resectable BTC at high risk for recurrence.
  
        High risk for recurrence, for which patients will be eligible for study, is defined by the
        presence of at least one of the following risk features, as evaluated at baseline
        (pre-surgery):
  
          1. For cholangiocarcinoma:
  
               -  Suspected or definite locoregional lymph node involvement in the absence of
                  jaundice (at least one of the following):
  
                    -  positive FNA cytology (obtained by EUS).
  
                    -  positive locoregional lymph nodes at PET-CT.
  
                    -  suspected positive locoregional lymph nodes at imaging (CT or MRI scan)
                       according to local MTD discussion (eg. short axis > 1.5 cm, contrast
                       enhancement uptake, round shape, restriction at DWI).
  
               -  Macrovascular invasion at preoperative CT scan.
  
               -  Expected R1 resection due to proximity to major intrahepatic vascular and biliary
                  structures.
  
               -  For iCCA, presence of satellitosis or multifocal disease or radiological suspicion
                  of tumoral diaphragmatic adhesion.
  
               -  For iCCA, size of the liver lesion >5 cm.
  
               -  For eCCA, size of the primary lesion > 3cm.
  
               -  Ca19.9 >100 U/mL.
  
          2. For GBC:
  
               -  Incidentally Detected Gallbladder Carcinoma (IGBC) After Simple Cholecystectomy
                  with indication for radical second surgery (>pT2) or newly diagnosed GBC.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Prospective, open-label, multicenter, randomized phase II-III study
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 12-month progression-free survival (PFS) rate
  time frame: 12 months
  description: the proportion of patients alive and free from progression/post-resection recurrence by 12-months timepoint from randomization (to be considered as primary endpoint in the phase II part of the study and as secondary endpoint in the phase III part of the study).
  measure: median PFS
  time frame: From date of randomization until the date of first documented progression (as assessed by radiological evaluation and clinical examination) or date of death from any cause, whichever came first, assessed up to 120 months
  description: i.e. the time from randomization to disease progression, post-resection recurrence or death from any cause (to be considered as secondary endpoint in the phase II part of the study and as primary endpoint in the phase III part of the study).
  measure: Median event free survival
  time frame: from date of randomization to date of disease progression that precludes definitive surgery, of treatment discontinuation for any reason, of post-resection recurrence, of diagnosis of a second primary cancer, or of death from any cause
  description: i.e. the time from randomization to disease progression that precludes definitive surgery, treatment discontinuation for any reason, post-resection recurrence, a second primary cancer, or death from any cause.
  measure: Median relapse free survival
  time frame: from date of surgery to date of disease recurrence or date of death, whichever came first, in patients who undergo surgery with curative intent, assessed up to 120 months.
  description: i.e. the time from surgery to disease recurrence or death in patients who undergo to surgery with curative intent.
  measure: Median Overall survival
  time frame: from date of randomization to date of death (or last follow up for alive patients), assessed up to 120 months.
  description: i.e. the time from randomization to death or last follow-up for alive patients.
  measure: R0 resection rate
  time frame: At surgery
  description: i.e. the percentage of patients, relative to the total of randomized patients, for whom a R0 resection is achieved.
  measure: R0+R1 resection rate
  time frame: At surgery
  description: i.e. the percentage of patients, relative to the total of randomized patients, for whom the tumor was macroscopically removed and the intent of surgery is considered curative.
  measure: Quality of life EORTC QLQ-C30 scores
  time frame: Quality of life questionnaires will be compiled during screening (28 days before randomisation) and at restaging before (week 8 to 10 after randomisation) and after surgery (week 6 to 16 after surgery)
  description: QoL will be estimated with EORTC QLQ-C30; mean score changes from baseline, proportion of patients with improved, stable, or deteriorated scores from baseline and time to deterioration in the EORTC QLQ-C30 scores will be compared between the two arms. Time to deterioration will be defined as the time from baseline to the first onset of a 10-point or greater decrease (for functional scales)/increase (for symptoms scale) from baseline, with confirmation under the right-censoring rule. All available observations will be used to calculate time to deterioration.
  measure: Quality of life BIL21 scores
  time frame: Quality of life questionnaires will be compiled during screening (28 days before randomisation) and at restaging before (week 8 to 10 after randomisation) and after surgery (week 6 to 16 after surgery)
  description: QoL will be estimated with the module BIL21; mean score changes from baseline, proportion of patients with improved, stable, or deteriorated scores from baseline and time to deterioration in the BIL21 physical functioning, social functioning, and fatigue scores will be compared between the two arms. Time to deterioration was defined as the time from baseline to the first onset of a 10-point or greater decrease from baseline for functional scales or a 10-point or greater increase for symptom scales, with confirmation under the right-censoring rule. All available observations will be used to calculate time to deterioration.
  measure: Overall response rate
  time frame: At radiological evaluation as performed at restaging before surgery (week 8 to 10 after randomisation)
  description: of neoadjuvant therapy as per investigator assessment and central review, i.e. the percentage of patients, relative to the total of enrolled subjects receiving neoadjuvant treatment, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria.
  measure: Resectability rate of primary tumor
  time frame: Resectability rate will be assessed before surgery (after the 3 cycles of neoadjuvant chemotherapy for the experimental treatment arm)
  description: i.e. the retrospective evaluation of patients with unresectable disease, as assessed by the central review committee, in the two arms, and of the rate of conversion to resectability in the neoadjuvant arm.
  measure: Toxicity rates
  time frame: Through study completion, an average of 1 year for each patient
  description: .e. the percentage of patients, relative to the total of subjects randomized to neoadjuvant treatment, experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0).
  measure: Perioperative morbidity and mortality
  time frame: At surgery
  description: i.e. the percentage of patients, relative to the total of enrolled subjects undergoing surgery, with any serious perioperative morbidity or mortality according to Clavien-Dindo classification.
  arm group label: Preoperative chemotherapy
  arm group type: Experimental
  description: Triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment followed by surgery and adjuvant chemotherapy
  arm group label: Upfront surgery
  arm group type: Active Comparator
  description: Standard upfront surgery and adjuvant chemotherapy
  intervention type: Drug
  intervention name: Gemcitabine
  description: ◦ Gemcitabine 800 mg/mq iv, day 1 and 8 of 21-day cycles, for 3 cycles
  arm group label: Preoperative chemotherapy
  intervention type: Drug
  intervention name: Nab paclitaxel
  description: ◦ Nab-paclitaxel 100 mg/mq, day 1 and 8 of 21-day cycles, for 3 cycles
  arm group label: Preoperative chemotherapy
  other name: Abraxane
  intervention type: Drug
  intervention name: Cisplatin
  description: ◦ Cisplatin 25 mg/mq iv, day 1 and 8 of 21-day cycles, for 3 cycles
  arm group label: Preoperative chemotherapy
  intervention type: Procedure
  intervention name: Curative Surgery
  description: Curative surgery on primary tumor
  arm group label: Preoperative chemotherapy
  arm group label: Upfront surgery
  intervention type: Drug
  intervention name: Capecitabine
  description: 1250 mg/m2 given orally twice daily on days 1 to 14 of a 3 weekly cycle for a total of 8 cycles
  arm group label: Preoperative chemotherapy
  arm group label: Upfront surgery
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Monica Niger, MD
  role: Principal Investigator
  affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
  last name: Monica Niger, MD
  role: Principal Investigator
  affiliation: 02 2390 2919
  last name: Monica Niger, MD
  phone: 02 2390 2919
  email: monica.niger@istitutotumori.mi.it
  last name: Federico Nichetti, MD
  phone: 02 2390 3586
  email: PURITYstudy@istitutotumori.mi.it
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  country: Italy
  citation: Yadav S, Xie H, Bin-Riaz I, Sharma P, Durani U, Goyal G, Borah B, Borad MJ, Smoot RL, Roberts LR, Go RS, McWilliams RR, Mahipal A. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis. Eur J Surg Oncol. 2019 Aug;45(8):1432-1438. doi: 10.1016/j.ejso.2019.03.023. Epub 2019 Mar 21.
  PMID: 30914290
  citation: Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, Raghav KPS, Iwasaki M, Masci P, Ramanathan RK, Ahn DH, Bekaii-Saab TS, Borad MJ. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):824-830. doi: 10.1001/jamaoncol.2019.0270.
  PMID: 30998813
  citation: Maithel SK, Keilson JM, Cao HST, Rupji M, Mahipal A, Lin BS, Javle MM, Cleary SP, Akce M, Switchenko JM, Rocha FG. NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2023 Jun 27. doi: 10.1245/s10434-023-13809-5. Online ahead of print.
  PMID: 37368098
  responsible party type: Sponsor
  mesh term: Cholangiocarcinoma
  mesh term: Biliary Tract Neoplasms
  mesh term: Recurrence
  mesh term: Paclitaxel
  mesh term: Gemcitabine
  mesh term: Capecitabine
  sharing ipd: No