<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/NCT04422392</url>
  </required_header>
  <id_info>
    <org_study_id>NALAN-01</org_study_id>
    <nct_id>NCT04422392</nct_id>
  </id_info>
  <brief_title>Neoadjuvant PD-1 Antibody Plus Chemotherapy in Resectable Stage IIIA-N2 Non-Small-Cell Lung Cancer</brief_title>
  <official_title>Neoadjuvant PD-1 Antibody Plus Chemotherapy in Resectable Stage IIIA-N2 Non-Small-Cell Lung Cancer: A Randomized Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Pulmonary Hospital, Shanghai, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Pulmonary Hospital, Shanghai, China</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, open label study designed to evaluate the efficacy and safety of&#xD;
      neoadjuvant PD-1 antibody plus chemotherapy followed by surgery in resectable stage IIIA-N2&#xD;
      non-small cell lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, randomised, two-arm, phase II, multi-centre clinical trial. The&#xD;
      proposed study will evaluate the efficacy and safety of preoperative administration PD-1&#xD;
      antibody plus chemotherapy in patients resectable stage IIIA-N2 NSCLC. Data obtained in this&#xD;
      study will provide valuable information for planning further phase III clinical trials of&#xD;
      anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease&#xD;
      setting.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    since the CheckMate816 study is published in NEJM, enrolling patients becomes difficult&#xD;
  </why_stopped>
  <start_date type="Actual">July 13, 2020</start_date>
  <completion_date type="Actual">September 30, 2022</completion_date>
  <primary_completion_date type="Actual">September 30, 2022</primary_completion_date>
  <phase>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>PFS at 24 months</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.</time_frame>
    <description>The PFS is defined as the time from diagnosis to relapse, progression or death, whichever occurred first.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">93</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant PD-1 antibody puls chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neoadjuvant treatment (PD-1 antibody+carboplatin+pemetrexed or nab-paclitaxel ) will start within 1-3 days from enrollment. 3 cycles will be administered at 21-day (+/- 3 days) intervals (QW3) prior to surgery. Before surgery a tumor assessment will be done. Patients with stable disease or partial response may be considered for surgery.&#xD;
Surgery: Surgery must be done within the 4rd-6th week from day 1 cycle 3 of neoadjuvant treatment (day 29-43 after day 1 of cycle 3) Adjuvant treatment: Patients that are R0 confirmed by surgical pathology evaluation will receive the first adjuvant administration within the 2rd to 8th week from surgery. Three cycles of combinded adjuvant treatment (PD-1 antibody+carboplatin+pemetrexed or nab-paclitaxel ) will be administered. Thirteen cycles of PD-1 antibody will start within day 21-24 days from day 1 of adjuvant cycle 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Neoadjuvant chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Neoadjuvant treatment (carboplatin+pemetrexed or nab-paclitaxel ) will start within 1-3 days from enrollment/randomisation. 3 cycles will be administered at 21-day (+/- 3 days) intervals (QW3) prior to surgery. Before surgery a tumor assessment will be done. Patients must leave the study if there is evidence of progression. Patients with stable disease or partial response may be considered for surgery.&#xD;
Surgery: Surgery must be done within the 4rd-6th week from day 1 cycle 3 of neoadjuvant treatment (day 29-43 after day 1 of cycle 3).&#xD;
Adjuvant treatment: Patients that are R0 confirmed by surgical pathology evaluation will receive the first adjuvant administration within the 2rd to 8th week from surgery. Three cycles of adjuvant treatment (carboplatin+pemetrexed or nab-paclitaxel ) will be administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>(IV, Q3W)</description>
    <arm_group_label>Neoadjuvant PD-1 antibody puls chemotherapy</arm_group_label>
    <arm_group_label>Neoadjuvant chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed or Nab-paclitaxel</intervention_name>
    <description>Pemetrexed (Nonsquamous NSCLC) or Nab-paclitaxel (Squamous NSCLC) (IV, Q3W)</description>
    <arm_group_label>Neoadjuvant PD-1 antibody puls chemotherapy</arm_group_label>
    <arm_group_label>Neoadjuvant chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-1 antibody</intervention_name>
    <description>(IV, Q3W)</description>
    <arm_group_label>Neoadjuvant PD-1 antibody puls chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent provided.&#xD;
&#xD;
          -  Males or females aged ≥18 years.&#xD;
&#xD;
          -  Pathologically diagnosed of non-small cell lung cancer.&#xD;
&#xD;
          -  Diagnosed as stage IIIA- N2.The diagnosis standard of N2 is as below: Pts with&#xD;
             resectable stage IIIA-N2 NSCLC confirmed by mediastinoscopy or EBUS and PET/CT.&#xD;
&#xD;
          -  Tumor should be considered resectable before study entry by a multidisciplinary team.&#xD;
&#xD;
          -  ECOG (Performance status) 0-1.&#xD;
&#xD;
          -  Screening laboratory values must meet the following criteria and should be obtained&#xD;
             within 7 days prior to randomization.&#xD;
&#xD;
             i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 x×109/L iii. Hemoglobin &gt; 9.0 g/dL iv.&#xD;
             Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min v. AST/ALT ≤ 3&#xD;
             x ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can&#xD;
             have total bilirubin &lt; 3.0 mg/dL) vii. The patients need to have a forced expiratory&#xD;
             volume (FEV1) ≥ 1.2 liters or &gt;40% predicted value viii. INR/APTT within normal&#xD;
             limits.&#xD;
&#xD;
          -  Women of childbearing potential, including women who had their last menstrual period&#xD;
             in the last 2 years, must have a negative serum or urine pregnancy test within 7 days&#xD;
             before randomization.&#xD;
&#xD;
          -  All sexually active men and women of childbearing potential must use an effective&#xD;
             contraceptive method (two barrier methods or a barrier method plus a hormonal method)&#xD;
             during the study treatment and for a period of at least 12 months following the last&#xD;
             administration of trial drugs.&#xD;
&#xD;
          -  Patient capable of proper therapeutic compliance and accessible for correct follow-up.&#xD;
&#xD;
          -  Measurable or evaluable disease (according to RECIST 1.1 criteria).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All patients carrying activating mutations in the TK domain of EGFR or any variety of&#xD;
             alterations in the ALK gene.&#xD;
&#xD;
          -  Patients with a condition requiring systemic treatment with either corticosteroids&#xD;
             (&gt;10 mg daily prednisone equivalent) or other immunosuppressive medications within 14&#xD;
             days of randomization. Inhaled or topical steroids, and adrenal replacement steroid&#xD;
             doses &gt; 10 mg daily prednisone equivalent, are permitted in the absence of active&#xD;
             autoimmune disease.&#xD;
&#xD;
          -  Patients with a history of interstitial lung disease cannot be included if they have&#xD;
             symptomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contact&#xD;
             trial team.&#xD;
&#xD;
          -  Patients with other active malignancy requiring concurrent intervention and/or&#xD;
             concurrent treatment with other investigational drugs or anti-cancer therapy.&#xD;
&#xD;
          -  Patients with previous malignancies (except non-melanoma skin cancers, and the&#xD;
             following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia,&#xD;
             melanoma, or breast) are excluded unless a complete remission was achieved at least 2&#xD;
             years prior to study entry AND no additional therapy is required during the study&#xD;
             period.&#xD;
&#xD;
          -  Any medical, mental or psychological condition which in the opinion of the&#xD;
             investigator would not permit the patient to complete the study or understand the&#xD;
             patient information.&#xD;
&#xD;
          -  Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2,&#xD;
             anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell&#xD;
             costimulation or immune checkpoint pathways.&#xD;
&#xD;
          -  Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or&#xD;
             hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic&#xD;
             infection.&#xD;
&#xD;
          -  Patients with known history of testing positive for human immunodeficiency virus (HIV)&#xD;
             or known acquired immunodeficiency syndrome (AIDS).&#xD;
&#xD;
          -  Patients with history of allergy to study drug components excipients.&#xD;
&#xD;
          -  Women who are pregnant or in the period of breastfeeding.&#xD;
&#xD;
          -  Sexually active men and women of childbearing potential who are not willing to use an&#xD;
             effective contraceptive method during the study.&#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>Chang Chen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Pulmonary Hospital, School of Medicine, Tongji University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First Hospital of Lanzhou University</name>
      <address>
        <city>Lanzhou</city>
        <state>Gansu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Soochow University</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changzheng Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changhai Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200092</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200092</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Pulmonary Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200092</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shuguang Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200092</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhejiang Cancer Hospita</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>August 27, 2023</last_update_submitted>
  <last_update_submitted_qc>August 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Pulmonary Hospital, Shanghai, China</investigator_affiliation>
    <investigator_full_name>Chang Chen</investigator_full_name>
    <investigator_title>Vice-president of Shanghai Pulmonary Hospital,</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <mesh_term>Antibodies</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04422392
org study id: NALAN-01
nct id: NCT04422392
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a randomized, open label study designed to evaluate the efficacy and safety of
      neoadjuvant PD-1 antibody plus chemotherapy followed by surgery in resectable stage IIIA-N2
      non-small cell lung cancer.
This is an open-label, randomised, two-arm, phase II, multi-centre clinical trial. The
      proposed study will evaluate the efficacy and safety of preoperative administration PD-1
      antibody plus chemotherapy in patients resectable stage IIIA-N2 NSCLC. Data obtained in this
      study will provide valuable information for planning further phase III clinical trials of
      anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease
      setting.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS at 24 months
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
description: The PFS is defined as the time from diagnosis to relapse, progression or death, whichever occurred first.
arm group label: Neoadjuvant PD-1 antibody puls chemotherapy
arm group type: Experimental
description: Neoadjuvant treatment (PD-1 antibody+carboplatin+pemetrexed or nab-paclitaxel ) will start within 1-3 days from enrollment. 3 cycles will be administered at 21-day (+/- 3 days) intervals (QW3) prior to surgery. Before surgery a tumor assessment will be done. Patients with stable disease or partial response may be considered for surgery.
Surgery: Surgery must be done within the 4rd-6th week from day 1 cycle 3 of neoadjuvant treatment (day 29-43 after day 1 of cycle 3) Adjuvant treatment: Patients that are R0 confirmed by surgical pathology evaluation will receive the first adjuvant administration within the 2rd to 8th week from surgery. Three cycles of combinded adjuvant treatment (PD-1 antibody+carboplatin+pemetrexed or nab-paclitaxel ) will be administered. Thirteen cycles of PD-1 antibody will start within day 21-24 days from day 1 of adjuvant cycle 2.
arm group label: Neoadjuvant chemotherapy
arm group type: Active Comparator
description: Neoadjuvant treatment (carboplatin+pemetrexed or nab-paclitaxel ) will start within 1-3 days from enrollment/randomisation. 3 cycles will be administered at 21-day (+/- 3 days) intervals (QW3) prior to surgery. Before surgery a tumor assessment will be done. Patients must leave the study if there is evidence of progression. Patients with stable disease or partial response may be considered for surgery.
Surgery: Surgery must be done within the 4rd-6th week from day 1 cycle 3 of neoadjuvant treatment (day 29-43 after day 1 of cycle 3).
Adjuvant treatment: Patients that are R0 confirmed by surgical pathology evaluation will receive the first adjuvant administration within the 2rd to 8th week from surgery. Three cycles of adjuvant treatment (carboplatin+pemetrexed or nab-paclitaxel ) will be administered.
intervention type: Drug
intervention name: Carboplatin
description: (IV, Q3W)
arm group label: Neoadjuvant PD-1 antibody puls chemotherapy
arm group label: Neoadjuvant chemotherapy
intervention type: Drug
intervention name: Pemetrexed or Nab-paclitaxel
description: Pemetrexed (Nonsquamous NSCLC) or Nab-paclitaxel (Squamous NSCLC) (IV, Q3W)
arm group label: Neoadjuvant PD-1 antibody puls chemotherapy
arm group label: Neoadjuvant chemotherapy
intervention type: Drug
intervention name: PD-1 antibody
description: (IV, Q3W)
arm group label: Neoadjuvant PD-1 antibody puls chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chang Chen, MD, PhD
role: Principal Investigator
affiliation: Shanghai Pulmonary Hospital, School of Medicine, Tongji University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Pulmonary Hospital, Shanghai, China
investigator full name: Chang Chen
investigator title: Vice-president of Shanghai Pulmonary Hospital,
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Pemetrexed
mesh term: Antibodies