<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/NCT02980991</url>
  </required_header>
  <id_info>
    <org_study_id>PCPOII</org_study_id>
    <nct_id>NCT02980991</nct_id>
  </id_info>
  <brief_title>Pemetrexed and Platinum Use in the Neoadjuvant Setting for Resectable Stage II and IIIA Lung Adenocarcinoma (ECTOP-1002)</brief_title>
  <official_title>Pemetrexed and Platinum Use in the Neoadjuvant Setting for Resectable Stage II and IIIA Lung Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a clinical trial from Eastern Cooperative Thoracic Oncology Project (ECTOP), numbered&#xD;
      as ECTOP-1002. The study is a prospective, single-center, open-label, single-armed, phase II&#xD;
      clinical trial. The aim of the study is to evaluate the radiological response rate (RR) of 2&#xD;
      cycles of neoadjuvant chemotherapy with pemetrexed and cisplatin in patients with resectable&#xD;
      stage II and IIIA lung adenocarcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a prospective, single-center, open-label, single-armed, phase II clinical trial.&#xD;
      Clinical staging is determined according to the routine protocol, which include enhanced&#xD;
      chest CT scans, brain MRI or CT, bone scintigraphy, abdominal ultrasonography and&#xD;
      cardiopulmonary tests. PET/CT scan was optional. Preoperative diagnoses of lymph node&#xD;
      metastasis were performed using enhanced chest CT or PET/CT. Preoperative pathological&#xD;
      diagnosis is confirmed by electronic fiber bronchoscopic biopsy, CT-guided percutaneous lung&#xD;
      puncture biopsy and endobronchial ultrasonography （EBUS/EUS） when necessary.&#xD;
&#xD;
      Patients are going to receive two cycles of pemetrexed 500mg/m2 day 1 and cisplatin 75mg/m2&#xD;
      day 1 (or 25mg/m2 day 1-3), 21 days per cycle. Treatment cycles are repeated every 21 days.&#xD;
      Following two cycles of chemotherapy, the same radiological examination as baseline chest CT&#xD;
      or PET/CT scans are repeated for tumor response evaluation. Radiographic response was&#xD;
      recorded by Response Evaluation Criteria in Solid Tumors （RECIST 1.1）. Patients undergo&#xD;
      complete resection between 2 and 6weeks following the last dose of chemotherapy. The surgical&#xD;
      extents left to the discretion of the general thoracic surgeon. And lobectomy and&#xD;
      pneumonectomy with mediastinal lymph node dissection are recommended. Two cycles of&#xD;
      post-surgery pemetrexed/cisplatin treatment will be administrated subsequently.&#xD;
&#xD;
      The primary objective is to determine the radiological response rate (RR) of 2 cycles of&#xD;
      neoadjuvant chemotherapy with pemetrexed and cisplatin in patients with resectable stage II&#xD;
      and IIIA lung adenocarcinoma. The radiological response rate is measured 3 to 4 weeks after&#xD;
      the second cycle of chemotherapy according to the RECIST criteria 1.1.&#xD;
&#xD;
      The secondary objectives are to determine the pathological response rate, safety, the&#xD;
      clinical feasibility rate, the drug delivery, 2-year disease free survival (DFS) and 2-year&#xD;
      overall survival (OS).The pathological response rate is investigated by determination of the&#xD;
      type and extent of vital tumor tissue and tumor necroses as well as reactive alterations with&#xD;
      foam cell reaction and fibrosis or scar formation on light microscopic evaluation of surgical&#xD;
      resection specimens stained with H&amp;E.The clinical feasibility is achieved if 1) no death due&#xD;
      to cancer, toxicity or comorbidity,and 2) no toxicity events including Grade 4 neutropenia &gt;7&#xD;
      days; febrile grade 3/4 neutropenia; grade 4 thrombocytopenia &gt;7 days or any grade with&#xD;
      bleeding; grade 3/4 nonhematologic toxicity related to chemotherapy (except&#xD;
      nausea/vomiting/hair loss) are observed. The drug delivery is defined as the accomplishment&#xD;
      of the chemotherapy.DFS is measured from the date of operation until the date of first&#xD;
      progression or recurrence. OS is measured from the date of operation until the date of death&#xD;
      from NSCLC or the date last seen alive.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2015</start_date>
  <completion_date type="Actual">April 2018</completion_date>
  <primary_completion_date type="Actual">January 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</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>radiological response rate</measure>
    <time_frame>Three to four weeks after the second cycle of neoadjuvant chemotherapy</time_frame>
    <description>Three to four weeks after the first cycle of neoadjuvant chemotherapy, the same radiological examination as baseline chest CT or PET/CT scans are repeated for tumor response evaluation. Radiographic response was recorded by RECIST 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events of chemotherapy</measure>
    <time_frame>ten months after neoadjuvant chemotherapy</time_frame>
    <description>1) death due to cancer, toxicity or comorbidity,and 2) toxicity events including Grade 4 neutropenia &gt;7 days; febrile grade 3/4 neutropenia; grade 4 thrombocytopenia &gt;7 days or any grade with bleeding; grade 3/4 nonhematologic toxicity related to chemotherapy (except nausea/vomiting/hair loss)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Lung Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant chemotherapy group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two cycles of pemetrexed and cisplatin given to patients before surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Two cycles of pemetrexed 500mg/m2 day 1, 21 days per cycle for patients before surgery</description>
    <arm_group_label>Neoadjuvant chemotherapy group</arm_group_label>
    <other_name>Neoadjuvant chemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Two cycles of cisplatin 75mg/m2 day 1 (or 25mg/m2 day 1-3), 21 days per cycle for patients before surgery</description>
    <arm_group_label>Neoadjuvant chemotherapy group</arm_group_label>
    <other_name>Neoadjuvant chemotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed consent must be signed.&#xD;
&#xD;
          2. At least 18 years of age.&#xD;
&#xD;
          3. Histologically or cytologically diagnosed as lung adenocarcinoma.&#xD;
&#xD;
          4. Have measurable and clinical stage II-IIIA (excluding superior sulcus) disease&#xD;
             eligible for surgery.&#xD;
&#xD;
          5. No previous systematic therapy or radiotherapy.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          7. Have a predicted postresection forced expiratory volume in 1 second (FEV1) of ≧1.0 L.&#xD;
&#xD;
          8. Have adequate organ function including the following:&#xD;
&#xD;
             Bone marrow: absolute neutrophil count (ANC) ≥1.5*109/L, platelets ≥100*109/L,&#xD;
             hemoglobin ≥8 g/dL.&#xD;
&#xD;
             Hepatic: bilirubin ≤1.5 ULN, alkaline phosphatase (AP), aspartate transaminase (AST),&#xD;
             and alanine transaminase (ALT) ≤3.0 ULN.&#xD;
&#xD;
             Renal: calculated creatinine clearance ≥45 mL/min (using the standard Cockcroft-Gault&#xD;
             formula).&#xD;
&#xD;
          9. For women: must be surgically sterile, postmenopausal, or compliant with a medically&#xD;
             approved contraceptive regimen during and for 3 months after the treatment period;&#xD;
             must have negative serum or urine pregnancy test and must not be lactating. For men:&#xD;
             must be surgically sterile, or compliant with a contraceptive regimen during and for 3&#xD;
             months after the treatment period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have received treatment within the last 30 days with a drug that has not received&#xD;
             regulatory approval for any indication at the time of study entry or concurrent&#xD;
             administration of any other anti-tumor therapy.&#xD;
&#xD;
          2. Clinically diagnosed as stage I or IIIB.&#xD;
&#xD;
          3. Have history of another malignancy within the last 5 years except cured carcinoma&#xD;
             in-situ of uterine cervix, cured basal cell carcinoma of skin and superficial bladder&#xD;
             tumors [Ta, Tis &amp; T1].&#xD;
&#xD;
          4. Concurrent use of any other anti-cancer therapy during study treatment.&#xD;
&#xD;
          5. Any unstable systemic disease (including active infection, hepatic, renal or metabolic&#xD;
             disease) or serious concomitant disorders that would compromise the safety of the&#xD;
             patient, or compromise the patient's ability to complete the study, at the discretion&#xD;
             of the investigator.&#xD;
&#xD;
          6. Significant cardiovascular event: congestive heart failure &gt; New York Heart&#xD;
             Association (NYHA) class 2; unstable angina, active CAD (myocardial infarction more&#xD;
             than 1 year prior to study entry is allowed); serious cardiac arrhythmia requiring&#xD;
             anti-arrythmic therapy (beta-blockers or digoxin are permitted) or uncontrolled&#xD;
             hypertension.&#xD;
&#xD;
          7. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)&#xD;
             2 days before, the day of, and 2 days after the dose of pemetrexed. If a patient is&#xD;
             taking an NSAID (Cox-2 inhibitors included) or salicylate with a long half-life (e.g.&#xD;
             naproxen, piroxicam, diflusinal, nabumetone, rofecoxib, or celecoxib) it should not be&#xD;
             taken 5 days before, the day of, and 2 days after the dose of pemetrexed.&#xD;
&#xD;
          8. Inability or unwillingness to take folic acid, vitamin B12 supplementation, or&#xD;
             dexamethasone.&#xD;
&#xD;
          9. Inability to comply with protocol or study procedures.&#xD;
&#xD;
         10. Pregnant or breast-feeding women and childbearing potential women with either a&#xD;
             positive or no pregnancy test within 48 hours of the start of treatment.&#xD;
             Postmenopausal women must have been amenorrhoeic for at least 12 months to be&#xD;
             considered of non-childbearing potential.&#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>Haiquan Chen, M.D, PH.D</last_name>
    <role>Study Chair</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 16, 2014</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Haiquan Chen</investigator_full_name>
    <investigator_title>Director of Department of Thoracic Surgery, Shanghai Cancer Center</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Adenocarcinoma of Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pemetrexed</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02980991
org study id: PCPOII
nct id: NCT02980991
lead sponsor: 
has dmc: No
This is a clinical trial from Eastern Cooperative Thoracic Oncology Project (ECTOP), numbered
      as ECTOP-1002. The study is a prospective, single-center, open-label, single-armed, phase II
      clinical trial. The aim of the study is to evaluate the radiological response rate (RR) of 2
      cycles of neoadjuvant chemotherapy with pemetrexed and cisplatin in patients with resectable
      stage II and IIIA lung adenocarcinoma.
The study is a prospective, single-center, open-label, single-armed, phase II clinical trial.
      Clinical staging is determined according to the routine protocol, which include enhanced
      chest CT scans, brain MRI or CT, bone scintigraphy, abdominal ultrasonography and
      cardiopulmonary tests. PET/CT scan was optional. Preoperative diagnoses of lymph node
      metastasis were performed using enhanced chest CT or PET/CT. Preoperative pathological
      diagnosis is confirmed by electronic fiber bronchoscopic biopsy, CT-guided percutaneous lung
      puncture biopsy and endobronchial ultrasonography （EBUS/EUS） when necessary.

      Patients are going to receive two cycles of pemetrexed 500mg/m2 day 1 and cisplatin 75mg/m2
      day 1 (or 25mg/m2 day 1-3), 21 days per cycle. Treatment cycles are repeated every 21 days.
      Following two cycles of chemotherapy, the same radiological examination as baseline chest CT
      or PET/CT scans are repeated for tumor response evaluation. Radiographic response was
      recorded by Response Evaluation Criteria in Solid Tumors （RECIST 1.1）. Patients undergo
      complete resection between 2 and 6weeks following the last dose of chemotherapy. The surgical
      extents left to the discretion of the general thoracic surgeon. And lobectomy and
      pneumonectomy with mediastinal lymph node dissection are recommended. Two cycles of
      post-surgery pemetrexed/cisplatin treatment will be administrated subsequently.

      The primary objective is to determine the radiological response rate (RR) of 2 cycles of
      neoadjuvant chemotherapy with pemetrexed and cisplatin in patients with resectable stage II
      and IIIA lung adenocarcinoma. The radiological response rate is measured 3 to 4 weeks after
      the second cycle of chemotherapy according to the RECIST criteria 1.1.

      The secondary objectives are to determine the pathological response rate, safety, the
      clinical feasibility rate, the drug delivery, 2-year disease free survival (DFS) and 2-year
      overall survival (OS).The pathological response rate is investigated by determination of the
      type and extent of vital tumor tissue and tumor necroses as well as reactive alterations with
      foam cell reaction and fibrosis or scar formation on light microscopic evaluation of surgical
      resection specimens stained with H&E.The clinical feasibility is achieved if 1) no death due
      to cancer, toxicity or comorbidity,and 2) no toxicity events including Grade 4 neutropenia >7
      days; febrile grade 3/4 neutropenia; grade 4 thrombocytopenia >7 days or any grade with
      bleeding; grade 3/4 nonhematologic toxicity related to chemotherapy (except
      nausea/vomiting/hair loss) are observed. The drug delivery is defined as the accomplishment
      of the chemotherapy.DFS is measured from the date of operation until the date of first
      progression or recurrence. OS is measured from the date of operation until the date of death
      from NSCLC or the date last seen alive.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: radiological response rate
time frame: Three to four weeks after the second cycle of neoadjuvant chemotherapy
description: Three to four weeks after the first cycle of neoadjuvant chemotherapy, the same radiological examination as baseline chest CT or PET/CT scans are repeated for tumor response evaluation. Radiographic response was recorded by RECIST 1.1.
measure: Number of Adverse Events of chemotherapy
time frame: ten months after neoadjuvant chemotherapy
description: 1) death due to cancer, toxicity or comorbidity,and 2) toxicity events including Grade 4 neutropenia >7 days; febrile grade 3/4 neutropenia; grade 4 thrombocytopenia >7 days or any grade with bleeding; grade 3/4 nonhematologic toxicity related to chemotherapy (except nausea/vomiting/hair loss)
arm group label: Neoadjuvant chemotherapy group
arm group type: Experimental
description: Two cycles of pemetrexed and cisplatin given to patients before surgery
intervention type: Drug
intervention name: Pemetrexed
description: Two cycles of pemetrexed 500mg/m2 day 1, 21 days per cycle for patients before surgery
arm group label: Neoadjuvant chemotherapy group
other name: Neoadjuvant chemotherapy
intervention type: Drug
intervention name: Cisplatin
description: Two cycles of cisplatin 75mg/m2 day 1 (or 25mg/m2 day 1-3), 21 days per cycle for patients before surgery
arm group label: Neoadjuvant chemotherapy group
other name: Neoadjuvant chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Haiquan Chen, M.D, PH.D
role: Study Chair
affiliation: Fudan University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Haiquan Chen
investigator title: Director of Department of Thoracic Surgery, Shanghai Cancer Center
mesh term: Adenocarcinoma
mesh term: Adenocarcinoma of Lung
mesh term: Pemetrexed
sharing ipd: Undecided