<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/NCT01730222</url>
  </required_header>
  <id_info>
    <org_study_id>PACT-19</org_study_id>
    <secondary_id>2012-001763-75</secondary_id>
    <nct_id>NCT01730222</nct_id>
  </id_info>
  <brief_title>A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma</brief_title>
  <acronym>PACT-19</acronym>
  <official_title>A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS San Raffaele</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS San Raffaele</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Four-drug combo yielded a statistically significant improvement in progression-free survival&#xD;
      and overall survival compared to gemcitabine in patients with advanced pancreatic&#xD;
      adenocarcinoma. Nab-Paclitaxel showed promising antitumor activity in patients with&#xD;
      pancreatic cancer. Given the synergism of taxanes with gemcitabine, fluoropyrimidines and&#xD;
      platinating agents the role of nab-Paclitaxel in a 4-drug regimen will be explored.&#xD;
&#xD;
      The aim of this trial is to determine the recommended dose of nab-paclitaxel in combination&#xD;
      with cisplatin, capecitabine, and gemcitabine, PAXG regimen (Phase I), and to evaluate the&#xD;
      feasibility and the activity of the PAXG regimen in patients with stage III and IV pancreatic&#xD;
      cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVES: PHASE I: to determine the recommended phase 2 dose of nab-paclitaxel in&#xD;
      combination with cisplatin, capecitabine, and gemcitabine.&#xD;
&#xD;
      PHASE II: to evaluate the feasibility and the activity of the PAXG regimen in terms of&#xD;
      6-months progression-free survival in patients with stage III and IV pancreatic cancer.&#xD;
&#xD;
      OUTLINE Phase I - dose finding single institution trial, followed by a randomized open label&#xD;
      multicenter phase II trial.&#xD;
&#xD;
      Phase II: Patients will be stratified by stage (III vs IV) and CA19.9 level (&lt; 10 x ULN&#xD;
      versus &gt;10 x ULN); Patients will be randomly assigned to receive PAXG (arm A) or&#xD;
      gemcitabine-nab-paclitaxel regimen (arm B).&#xD;
&#xD;
      Treatment plan (phase II):&#xD;
&#xD;
      Arm A: PAXG every 4 weeks (1 cycle): cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel&#xD;
      at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/&#xD;
      m2 on days 1 and 15.&#xD;
&#xD;
      Arm B: Gemcitabine + nab-paclitaxel every 4 weeks (1 cycle): gemcitabine at 1000 mg/m2 on&#xD;
      days 1, 8 and 15; nab-paclitaxel at 125 mg/mq on days 1, 8 and 15.&#xD;
&#xD;
      Treatment will be administered for a maximum of 6 cycles or until there is a clinical&#xD;
      benefit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">August 2017</completion_date>
  <primary_completion_date type="Actual">February 2017</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>first cycle toxicity for phase I part</measure>
    <time_frame>after one month from treatment start</time_frame>
    <description>Dose Limiting Toxicity definition: DLT will be defined as any of the following events attributable to the administered study drugs:&#xD;
Hematologic toxicity&#xD;
Grade ≥ 4 neutropenia lasting 7 days or more&#xD;
Grade ≥ 3 febrile neutropenia or fever of unknown origin ≥ 38.5°C&#xD;
Grade 4 thrombocytopenia&#xD;
Grade 3 thrombocytopenia which required transfusions&#xD;
Nausea or vomiting Grade ≥ 3 nausea or vomiting despite maximal antiemetic therapy&#xD;
Diarrhea Grade ≥ 3 diarrhea despite optimal management of the event&#xD;
Neurological toxicity Any Grade ≥ 2 neurological toxicity&#xD;
Other non-hematologic toxicity Any grade ≥ 3 toxicities or representing a shift by 2 grades from baseline (in case of abnormal baseline)&#xD;
Failure to recover Failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by &gt; 2 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>progression-free survival for phase II part, stage IV patients</measure>
    <time_frame>after 6 months from randomization</time_frame>
    <description>rate of progression-free patients at 6 months from randomization</description>
  </primary_outcome>
  <primary_outcome>
    <measure>resectability rate for phase II part, stage III patients</measure>
    <time_frame>after 4 and 6 months from treatment start</time_frame>
    <description>rate of resectable patients at at time of CT evaluation and multidisciplinary assessment after 4 and 6 months from treatment start</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>response rate</measure>
    <time_frame>every two months up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months</time_frame>
    <description>contrast enhanced CT scan tumor assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>biochemical response rate</measure>
    <time_frame>every month up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months</time_frame>
    <description>blood sample for CA19.9 assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>toxicity</measure>
    <time_frame>every two weeks up to 26 weeks during treatment</time_frame>
    <description>outpatients visits; laboratory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>From date of trial enrolment until the date of death from any cause, assessed every two weeks up to 26 weeks during treatment; every 2-3 months afterwards up to 60 months</time_frame>
    <description>outpatients visit; phone interviews</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>From date of trial enrolment until the date of documented progression or date of death from any cause, whichever came first, assessed every two months up to 6 months during treatment; every 2-3 months afterwards up to 60 months</time_frame>
    <description>contrast enhanced CT scan</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">137</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>PAXG regimen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15 every 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>gemcitabine + nab-paclitaxel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>gemcitabine at 1000 mg/ m2 on days 1, 8 and 15 every 4 weeks + nab-paclitaxel at 125 mg/ m2 on days 1, 8 and 15 every 4 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cisplatin</intervention_name>
    <description>cisplatin at 30 mg/m2 on days 1 and 15</description>
    <arm_group_label>PAXG regimen</arm_group_label>
    <other_name>cisplatino TEVA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>capecitabine</intervention_name>
    <description>capecitabine at 1250 mg/ m2 days 1-28</description>
    <arm_group_label>PAXG regimen</arm_group_label>
    <other_name>XELODA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>gemcitabine</intervention_name>
    <description>gemcitabine at 800 mg/ m2 on days 1 and 15 in arm A; at 1000 mg/m2 on days 1, 8 and 15 in arm B</description>
    <arm_group_label>PAXG regimen</arm_group_label>
    <arm_group_label>gemcitabine + nab-paclitaxel</arm_group_label>
    <other_name>Gemzar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nab-paclitaxel</intervention_name>
    <description>nab-paclitaxel at the recommended phase II dose day 1 and 15 in arm A; at 125 mg/m2 on days 1, 8 and 15 in arm B</description>
    <arm_group_label>PAXG regimen</arm_group_label>
    <arm_group_label>gemcitabine + nab-paclitaxel</arm_group_label>
    <other_name>abraxane</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologic diagnosis of pancreatic adenocarcinoma&#xD;
&#xD;
          -  Stage III or IV disease&#xD;
&#xD;
          -  Age &gt; 17 &lt; 76 years&#xD;
&#xD;
          -  Karnofsky Performance Status &gt; 50&#xD;
&#xD;
          -  Measurable disease (only for phase II part)&#xD;
&#xD;
          -  Adequate bone marrow (GB &gt; 3500/mm3, neutrophils &gt; 1500/mm3; platelets &gt; 100000/mm3;&#xD;
             hemoglobin &gt; 10 g/dl), liver (total bilirubin &lt; 2 mg/dL; SGOT e SGPT &lt; 3 UNL) and&#xD;
             kidney function (serum creatinin &lt; 1.5 mg/dL;)&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous chemotherapy&#xD;
&#xD;
          -  concurrent treatment with other experimental drugs&#xD;
&#xD;
          -  previous or concurrent malignancies at other sites with the exception of surgically&#xD;
             cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the skin&#xD;
             and of other neoplasms without evidence of disease at least from 5 years&#xD;
&#xD;
          -  symptomatic brain metastases&#xD;
&#xD;
          -  history of interstitial lung disease&#xD;
&#xD;
          -  presence of serious disease which can compromise safety (cardiac failure, previous&#xD;
             myocardial infarction within the prior 6 months, cardiac arrhythmia, history of&#xD;
             psychiatric disabilities)&#xD;
&#xD;
          -  pregnancy and lactating&#xD;
&#xD;
          -  History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).&#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>Michele Reni, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS S RAFFAELE</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRCCS S Raffaele</name>
      <address>
        <city>Milan</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>November 4, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>August 31, 2017</last_update_submitted>
  <last_update_submitted_qc>August 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS San Raffaele</investigator_affiliation>
    <investigator_full_name>Michele Reni</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>pancreatic adenocarcinoma</keyword>
  <keyword>stage III disease</keyword>
  <keyword>stage IV disease</keyword>
  <keyword>chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</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>


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/NCT01730222
org study id: PACT-19
secondary id: 2012-001763-75
nct id: NCT01730222
lead sponsor: 
has dmc: No
Four-drug combo yielded a statistically significant improvement in progression-free survival
      and overall survival compared to gemcitabine in patients with advanced pancreatic
      adenocarcinoma. Nab-Paclitaxel showed promising antitumor activity in patients with
      pancreatic cancer. Given the synergism of taxanes with gemcitabine, fluoropyrimidines and
      platinating agents the role of nab-Paclitaxel in a 4-drug regimen will be explored.

      The aim of this trial is to determine the recommended dose of nab-paclitaxel in combination
      with cisplatin, capecitabine, and gemcitabine, PAXG regimen (Phase I), and to evaluate the
      feasibility and the activity of the PAXG regimen in patients with stage III and IV pancreatic
      cancer.
OBJECTIVES: PHASE I: to determine the recommended phase 2 dose of nab-paclitaxel in
      combination with cisplatin, capecitabine, and gemcitabine.

      PHASE II: to evaluate the feasibility and the activity of the PAXG regimen in terms of
      6-months progression-free survival in patients with stage III and IV pancreatic cancer.

      OUTLINE Phase I - dose finding single institution trial, followed by a randomized open label
      multicenter phase II trial.

      Phase II: Patients will be stratified by stage (III vs IV) and CA19.9 level (< 10 x ULN
      versus >10 x ULN); Patients will be randomly assigned to receive PAXG (arm A) or
      gemcitabine-nab-paclitaxel regimen (arm B).

      Treatment plan (phase II):

      Arm A: PAXG every 4 weeks (1 cycle): cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel
      at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/
      m2 on days 1 and 15.

      Arm B: Gemcitabine + nab-paclitaxel every 4 weeks (1 cycle): gemcitabine at 1000 mg/m2 on
      days 1, 8 and 15; nab-paclitaxel at 125 mg/mq on days 1, 8 and 15.

      Treatment will be administered for a maximum of 6 cycles or until there is a clinical
      benefit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: first cycle toxicity for phase I part
time frame: after one month from treatment start
description: Dose Limiting Toxicity definition: DLT will be defined as any of the following events attributable to the administered study drugs:
Hematologic toxicity
Grade ≥ 4 neutropenia lasting 7 days or more
Grade ≥ 3 febrile neutropenia or fever of unknown origin ≥ 38.5°C
Grade 4 thrombocytopenia
Grade 3 thrombocytopenia which required transfusions
Nausea or vomiting Grade ≥ 3 nausea or vomiting despite maximal antiemetic therapy
Diarrhea Grade ≥ 3 diarrhea despite optimal management of the event
Neurological toxicity Any Grade ≥ 2 neurological toxicity
Other non-hematologic toxicity Any grade ≥ 3 toxicities or representing a shift by 2 grades from baseline (in case of abnormal baseline)
Failure to recover Failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by > 2 weeks.
measure: progression-free survival for phase II part, stage IV patients
time frame: after 6 months from randomization
description: rate of progression-free patients at 6 months from randomization
measure: resectability rate for phase II part, stage III patients
time frame: after 4 and 6 months from treatment start
description: rate of resectable patients at at time of CT evaluation and multidisciplinary assessment after 4 and 6 months from treatment start
measure: response rate
time frame: every two months up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
description: contrast enhanced CT scan tumor assessment
measure: biochemical response rate
time frame: every month up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
description: blood sample for CA19.9 assessment
measure: toxicity
time frame: every two weeks up to 26 weeks during treatment
description: outpatients visits; laboratory
measure: overall survival
time frame: From date of trial enrolment until the date of death from any cause, assessed every two weeks up to 26 weeks during treatment; every 2-3 months afterwards up to 60 months
description: outpatients visit; phone interviews
measure: Progression-free survival
time frame: From date of trial enrolment until the date of documented progression or date of death from any cause, whichever came first, assessed every two months up to 6 months during treatment; every 2-3 months afterwards up to 60 months
description: contrast enhanced CT scan
arm group label: PAXG regimen
arm group type: Experimental
description: cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15 every 4 weeks
arm group label: gemcitabine + nab-paclitaxel
arm group type: Active Comparator
description: gemcitabine at 1000 mg/ m2 on days 1, 8 and 15 every 4 weeks + nab-paclitaxel at 125 mg/ m2 on days 1, 8 and 15 every 4 weeks
intervention type: Drug
intervention name: cisplatin
description: cisplatin at 30 mg/m2 on days 1 and 15
arm group label: PAXG regimen
other name: cisplatino TEVA
intervention type: Drug
intervention name: capecitabine
description: capecitabine at 1250 mg/ m2 days 1-28
arm group label: PAXG regimen
other name: XELODA
intervention type: Drug
intervention name: gemcitabine
description: gemcitabine at 800 mg/ m2 on days 1 and 15 in arm A; at 1000 mg/m2 on days 1, 8 and 15 in arm B
arm group label: PAXG regimen
arm group label: gemcitabine + nab-paclitaxel
other name: Gemzar
intervention type: Drug
intervention name: nab-paclitaxel
description: nab-paclitaxel at the recommended phase II dose day 1 and 15 in arm A; at 125 mg/m2 on days 1, 8 and 15 in arm B
arm group label: PAXG regimen
arm group label: gemcitabine + nab-paclitaxel
other name: abraxane
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Michele Reni, MD
role: Principal Investigator
affiliation: IRCCS S RAFFAELE
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: IRCCS San Raffaele
investigator full name: Michele Reni
investigator title: Principal Investigator
mesh term: Adenocarcinoma
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Capecitabine
sharing ipd: No