<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/NCT03791151</url>
  </required_header>
  <id_info>
    <org_study_id>ASU309</org_study_id>
    <nct_id>NCT03791151</nct_id>
  </id_info>
  <brief_title>Pharmacogenetics in Non Small Cell Lung Cancer</brief_title>
  <official_title>Effect of Copper Transporter-1 Genetic Polymorphism on Platinum Based Chemotherapy Response in Advanced Non-Small Cell Lung Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ain Shams University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ain Shams University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study the effect of genetic polymorphism in the membrane copper transporter 1 protein [CTR1;&#xD;
      encoded by the solute carrier family 31 member 1 gene (SLC31A1 gene)] and its genetic&#xD;
      expression levels on the clinical outcome of cisplatin-based regimen used in the treatment of&#xD;
      Non-Small Cell Lung Cancer (NSCLC) in terms of :&#xD;
&#xD;
        -  Treatment response : partial response (PR) / complete response (CR) and Progression-free&#xD;
           survival (PFS)&#xD;
&#xD;
        -  Treatment resistance : stationary disease (SD) or progressed disease&#xD;
&#xD;
        -  Frequency and severity of regimen related toxicity&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The cisplatin-based regimen is an effective treatment for advanced NSCLC, showing significant&#xD;
      beneficial outcomes such as prolong survival, improve clinical symptoms, and improve quality&#xD;
      of life (QOL) . Although platinum-based therapy shows several benefits, but the five-year&#xD;
      survival rate still less than 20%.&#xD;
&#xD;
      Pt resistance is an inevitable occurrence with rare exception. Aside from germ cell tumors,&#xD;
      metastatic solid tumors are generally thought to be incurable with cytotoxic chemotherapy due&#xD;
      to the development of resistance and subsequent disease progression.&#xD;
&#xD;
      Despite the multifactorial nature of Cisplatin resistance, intracellular accumulation of Pt&#xD;
      appears to be a major source of drug resistance . Reduced intracellular drug accumulation is&#xD;
      one of the most consistently identified features of cisplatin-resistant cells.&#xD;
&#xD;
      Many evidences indicated that alteration of copper transporter protein 1 (CTR1) which is the&#xD;
      major plasma membrane transporter responsible for platinum uptake, was associated with&#xD;
      platinum sensitivity and toxicity.&#xD;
&#xD;
      Genetic polymorphisms of CTR1 also have effects to platinum treatment response. Therefore,&#xD;
      CTR1 might be a potential prognostic factor for survival in cancer patients underwent&#xD;
      chemotherapy and a treatment target for overcoming platinum resistance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Anticipated">November 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2019</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>1 Year</target_duration>
  <primary_outcome>
    <measure>Tumor response and resistance</measure>
    <time_frame>1 year</time_frame>
    <description>will be evaluated after the third (initial evaluation response) and the sixth (confirmation of initial response) chemotherapy cycle according to the new Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>1.5 years</time_frame>
    <description>defined as the time from day 1 of chemotherapy to the day of documented disease progression or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regimen related toxicity</measure>
    <time_frame>1.5 years</time_frame>
    <description>1. Hematologic toxicity (anemia, neutropenia, and thrombocytopenia) 2. Nephrotoxicity 3. Ototoxicity 4. Neurotoxicity</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Newly diagnosed with immunohistochemically and pathologically confirmed non- small cell&#xD;
        lung cancer (NSCLC).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Newly diagnosed with immunohistochemically and pathologically confirmed non- small&#xD;
             cell lung cancer (NSCLC).&#xD;
&#xD;
          2. ECOG PS 0-2.&#xD;
&#xD;
          3. Chemotherapy naïve.&#xD;
&#xD;
          4. Age &gt;18 years.&#xD;
&#xD;
          5. Adequate bone marrow reserve.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of central nervous system metastases.&#xD;
&#xD;
          2. Inadequate liver function (bilirubin &gt; 1.5 times upper normal limit [ULN] and alanine&#xD;
             transaminase [ALT] or aspartate transaminase [AST] &gt; 3.0 ULN or up to 5.0 UNL in the&#xD;
             presence of hepatic metastases).&#xD;
&#xD;
          3. Inadequate renal function (creatinine &gt; 1.25 times ULN, creatinine clearance &lt;&#xD;
             50mL/min).&#xD;
&#xD;
          4. Serious comorbid systemic disorder incompatible with the study.&#xD;
&#xD;
          5. Second primary malignancy (except in situ carcinoma of the cervix, adequately treated&#xD;
             basal cell carcinoma of the skin, T1 vocal cord cancer in remission, or prior&#xD;
             malignancy treated more than 5 years prior to enrollment without recurrence).&#xD;
&#xD;
          6. Pregnancy&#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_contact>
    <last_name>Yara Sayed</last_name>
    <phone>01067004796</phone>
    <phone_ext>+2</phone_ext>
    <email>yara.awes@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ain Shams University's Hospital</name>
      <address>
        <city>Cairo</city>
        <zip>11566</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ahmed A Nagy, lecturer</last_name>
      <phone>010273373313</phone>
      <phone_ext>+2</phone_ext>
      <email>ahmedalynagy@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/18996970</url>
    <description>The role of the mammalian copper transporter 1 in the cellular accumulation of platinum-based drugs.</description>
  </link>
  <reference>
    <citation>Blair BG, Larson CA, Safaei R, Howell SB. Copper transporter 2 regulates the cellular accumulation and cytotoxicity of Cisplatin and Carboplatin. Clin Cancer Res. 2009 Jul 1;15(13):4312-21. doi: 10.1158/1078-0432.CCR-09-0311. Epub 2009 Jun 9.</citation>
    <PMID>19509135</PMID>
  </reference>
  <reference>
    <citation>Roco A, Cayun J, Contreras S, Stojanova J, Quinones L. Can pharmacogenetics explain efficacy and safety of cisplatin pharmacotherapy? Front Genet. 2014 Nov 14;5:391. doi: 10.3389/fgene.2014.00391. eCollection 2014.</citation>
    <PMID>25452763</PMID>
  </reference>
  <reference>
    <citation>Xu X, Ren H, Zhou B, Zhao Y, Yuan R, Ma R, Zhou H, Liu Z. Prediction of copper transport protein 1 (CTR1) genotype on severe cisplatin induced toxicity in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 2012 Aug;77(2):438-42. doi: 10.1016/j.lungcan.2012.03.023. Epub 2012 Apr 17.</citation>
    <PMID>22516052</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>December 31, 2018</last_update_submitted>
  <last_update_submitted_qc>December 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ain Shams University</investigator_affiliation>
    <investigator_full_name>Yara Sayed Abdulwahid</investigator_full_name>
    <investigator_title>Clinical Pharmacist</investigator_title>
  </responsible_party>
  <keyword>Pharmacogenetics</keyword>
  <keyword>Lung cancer</keyword>
  <keyword>Cisplatin</keyword>
  <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>
  <!-- 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/NCT03791151
org study id: ASU309
nct id: NCT03791151
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Study the effect of genetic polymorphism in the membrane copper transporter 1 protein [CTR1;
      encoded by the solute carrier family 31 member 1 gene (SLC31A1 gene)] and its genetic
      expression levels on the clinical outcome of cisplatin-based regimen used in the treatment of
      Non-Small Cell Lung Cancer (NSCLC) in terms of :

        -  Treatment response : partial response (PR) / complete response (CR) and Progression-free
           survival (PFS)

        -  Treatment resistance : stationary disease (SD) or progressed disease

        -  Frequency and severity of regimen related toxicity
The cisplatin-based regimen is an effective treatment for advanced NSCLC, showing significant
      beneficial outcomes such as prolong survival, improve clinical symptoms, and improve quality
      of life (QOL) . Although platinum-based therapy shows several benefits, but the five-year
      survival rate still less than 20%.

      Pt resistance is an inevitable occurrence with rare exception. Aside from germ cell tumors,
      metastatic solid tumors are generally thought to be incurable with cytotoxic chemotherapy due
      to the development of resistance and subsequent disease progression.

      Despite the multifactorial nature of Cisplatin resistance, intracellular accumulation of Pt
      appears to be a major source of drug resistance . Reduced intracellular drug accumulation is
      one of the most consistently identified features of cisplatin-resistant cells.

      Many evidences indicated that alteration of copper transporter protein 1 (CTR1) which is the
      major plasma membrane transporter responsible for platinum uptake, was associated with
      platinum sensitivity and toxicity.

      Genetic polymorphisms of CTR1 also have effects to platinum treatment response. Therefore,
      CTR1 might be a potential prognostic factor for survival in cancer patients underwent
      chemotherapy and a treatment target for overcoming platinum resistance.
observational model: Cohort
time perspective: Prospective
measure: Tumor response and resistance
time frame: 1 year
description: will be evaluated after the third (initial evaluation response) and the sixth (confirmation of initial response) chemotherapy cycle according to the new Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
measure: Progression-free survival (PFS)
time frame: 1.5 years
description: defined as the time from day 1 of chemotherapy to the day of documented disease progression or death.
measure: Regimen related toxicity
time frame: 1.5 years
description: 1. Hematologic toxicity (anemia, neutropenia, and thrombocytopenia) 2. Nephrotoxicity 3. Ototoxicity 4. Neurotoxicity
Blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yara Sayed
phone: 01067004796
phone ext: +2
email: yara.awes@gmail.com
facility: 
status: Recruiting
contact: 
country: Egypt
url: https://www.ncbi.nlm.nih.gov/pubmed/18996970
description: The role of the mammalian copper transporter 1 in the cellular accumulation of platinum-based drugs.
citation: Blair BG, Larson CA, Safaei R, Howell SB. Copper transporter 2 regulates the cellular accumulation and cytotoxicity of Cisplatin and Carboplatin. Clin Cancer Res. 2009 Jul 1;15(13):4312-21. doi: 10.1158/1078-0432.CCR-09-0311. Epub 2009 Jun 9.
PMID: 19509135
citation: Roco A, Cayun J, Contreras S, Stojanova J, Quinones L. Can pharmacogenetics explain efficacy and safety of cisplatin pharmacotherapy? Front Genet. 2014 Nov 14;5:391. doi: 10.3389/fgene.2014.00391. eCollection 2014.
PMID: 25452763
citation: Xu X, Ren H, Zhou B, Zhao Y, Yuan R, Ma R, Zhou H, Liu Z. Prediction of copper transport protein 1 (CTR1) genotype on severe cisplatin induced toxicity in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 2012 Aug;77(2):438-42. doi: 10.1016/j.lungcan.2012.03.023. Epub 2012 Apr 17.
PMID: 22516052
responsible party type: Principal Investigator
investigator affiliation: Ain Shams University
investigator full name: Yara Sayed Abdulwahid
investigator title: Clinical Pharmacist
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung