<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/NCT03258151</url>
  </required_header>
  <id_info>
    <org_study_id>2016[1239]-2</org_study_id>
    <nct_id>NCT03258151</nct_id>
  </id_info>
  <brief_title>Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients</brief_title>
  <official_title>Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cui Yimin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University First Hospital</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>
      Taxanes are one of the most active agents in the treatment of many kinds of solid tumors,&#xD;
      mainly including paclitaxel and docetaxel. However, variability in toxicity and response&#xD;
      remains a major problem for patients receiving taxanes. It is general that there are many&#xD;
      factors for individual differences of drugs in clinical application, of which genetic factors&#xD;
      accounted for more than 20%. Toxicities of docetaxel, such as myelosuppression, neurotoxicity&#xD;
      or mucositis, were evaluated for possible relationship with pharmacogenetic polymorphisms in&#xD;
      several candidate gene and genome-wide association studies. Due to the levels of evidence of&#xD;
      those studies are low and lack of sufficient research data of Chinese, it has the important&#xD;
      significance in studying individual differences of docetaxel in toxicities, through the&#xD;
      pharmacogenomics research.&#xD;
&#xD;
      The aim of this study is to evaluating the association genetic polymorphisms with&#xD;
      docetaxel-based chemotherapy toxicities in chinese solid tumor patients. By detecting the&#xD;
      gene polymorphism, investigators intend to study the pharmacokinetic/pharmacogenomics (PK-PG)&#xD;
      correlation of docetaxel and provide scientific basis for precise medication guide for people&#xD;
      to use docetaxel.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 25, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">September 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of severe hematological toxicity</measure>
    <time_frame>At 1 year</time_frame>
    <description>The toxicity induced by docetaxel-based chemotherapy during observation time will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Patients with grade 3-4 adverse events will be considered as having severe toxicity. At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis. Hematological toxicity includes neutropenia, leukopenia, anemia and thrombocytopenia.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of other severe toxicities</measure>
    <time_frame>At 1 year</time_frame>
    <description>The other toxicities induced by docetaxel-based chemotherapy during observation time, including gastrointestinal toxicity, neurotoxicity etc., will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Toxicities with grade 3-4 will be considered as severe toxicity, except for severe neurotoxicity (grade 2-3). At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotyping</measure>
    <time_frame>Before chemotherapy</time_frame>
    <description>Collect blood specimen, then detect genotype by next generation sequencing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The kinds of the metabolites</measure>
    <time_frame>Pre-dose and 6 hours post-dose in the first cycle</time_frame>
    <description>Determine the metabolic profiles of docetaxel. This outcome is not applicable to patients retrospectively collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve [AUC]</measure>
    <time_frame>Pre-dose and 6 hours post-dose in the first cycle</time_frame>
    <description>Determine the AUC of docetaxel and its metabolites. This outcome is not applicable to patients retrospectively collected.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">2200</enrollment>
  <condition>Solid Tumors</condition>
  <condition>Docetaxel</condition>
  <condition>Drug-Related Side Effects and Adverse Reactions</condition>
  <condition>Pharmacogenetics</condition>
  <condition>Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>wild genotype</arm_group_label>
    <description>Through next generation sequencing, distinguish wild genotype of docetaxel</description>
  </arm_group>
  <arm_group>
    <arm_group_label>mutant genotype</arm_group_label>
    <description>Through next generation sequencing, distinguish mutant genotype of docetaxel</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>detection of genotype</intervention_name>
    <description>detection of genotype by next generation sequencing</description>
    <arm_group_label>mutant genotype</arm_group_label>
    <arm_group_label>wild genotype</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Chinese solid tumor patients with the treatment of docetaxel-based chemotherapy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any native Chinese men or women at least 18 years of age;&#xD;
&#xD;
          -  Sign informed consent of the research;&#xD;
&#xD;
          -  Have a histologic or cytologic diagnosis of solid tumor;&#xD;
&#xD;
          -  Will receive docetaxel-based chemotherapy; Or patients who received docetaxel&#xD;
             chemotherapy meet the inclusion and exclusion criteria of the research, and their&#xD;
             clinical information is complete to obtain;&#xD;
&#xD;
          -  Male and female patients with reproductive potential must use an approved&#xD;
             contraceptive method during and for 3 months after discontinuation of study treatment.&#xD;
             Women with childbearing potential must have a negative pregnancy test within 7 days&#xD;
             prior to study enrollment;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.&#xD;
&#xD;
          -  Have discontinued all previous therapies for cancer for at least 28 days prior to&#xD;
             study entry, and have recovered from the acute effects of therapy.&#xD;
&#xD;
          -  Have adequate organ function, including:&#xD;
&#xD;
               1. Bone marrow reserve:&#xD;
&#xD;
                    1. ANC≥1.5×109/L&#xD;
&#xD;
                    2. PLT≥100×109/L&#xD;
&#xD;
                    3. HGB≥10g/dL&#xD;
&#xD;
               2. Hepatic:&#xD;
&#xD;
                    1. Bilirubin ≤ 1.5ULN&#xD;
&#xD;
                    2. ALT, AST ≤2.5 ULN, ≤5ULN when liver metastases are known&#xD;
&#xD;
               3. Renal: Src ≤1.5mg/dl&#xD;
&#xD;
          -  Electrolytes: Patients may be entered into the study if, in the investigators'&#xD;
             opinion, any electrolyte disorders, including K&lt;3.4mEq/L, Ca&lt;8.4mEq/L, or Mg&lt;1.2mEq/L,&#xD;
             may be appropriately managed and stabilized by the time of the laboratory evaluation&#xD;
             prior to the chemotherapy. If electrolytes have not been stabilized during this time,&#xD;
             the patient will be discontinued from the study.&#xD;
&#xD;
          -  Have an estimated life expectancy, in the judgment of the investigator, which will&#xD;
             permit the patient to complete the PK phase and at least 2 cycle of the evaluation of&#xD;
             the toxicities.&#xD;
&#xD;
        Exclusion Criteria;&#xD;
&#xD;
          -  Serious concomitant systemic disorder, including active infection, which is&#xD;
             incompatible with the study (at the discretion of the investigator).&#xD;
&#xD;
          -  History of human immunodeficiency virus, hepatitis B, or hepatitis C infections.&#xD;
&#xD;
          -  Cardiac: Have a serious cardiac condition, such as myocardial infarction within 6&#xD;
             months, angina, or heart disease, as defined by the New York Heart Association Class&#xD;
             III or IV. It is recommended that patients with arrhythmias (persistent or paroxysmal&#xD;
             ventricular or supraventricular arrhythmias, including atrial fibrillation or&#xD;
             bradycardia (heart rate &lt;50 beats per minute))be excluded at the investigator's&#xD;
             discretion.&#xD;
&#xD;
          -  Known family history of unexplained sudden death.&#xD;
&#xD;
          -  Personal history of unexplained syncope within the last year.&#xD;
&#xD;
          -  Women who are breast feeding, lactating, or pregnant.&#xD;
&#xD;
          -  Patients with known allergies to docetaxel and its supplementary materials.&#xD;
&#xD;
          -  Drugs and herbal supplements that are known to be potent or moderate inhibitors or&#xD;
             inducers of cytochrome P450 (CYP)3A4 are specifically excluded. Foods that are known&#xD;
             to be potent or moderate inhibitors of CYP3A4 are also specifically excluded during&#xD;
             the study.&#xD;
&#xD;
          -  Patients receiving herbal regimens.&#xD;
&#xD;
          -  Use of drugs with narrow therapeutic windows that are also known substrates of CYP3A4.&#xD;
&#xD;
          -  Failure for any reason to satisfy the investigator for adequate fitness to&#xD;
             participated in 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>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Affiliated Hospital of Academy of Military Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100171</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fuling Center Hospital of Chongqing City</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>408000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital of China Medical University</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <zip>110001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The FIrst Affiliated Hospital of Wenzhou Medical University</name>
      <address>
        <city>Wenzhou</city>
        <state>Zhejiang</state>
        <zip>325000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>August 27, 2019</last_update_submitted>
  <last_update_submitted_qc>August 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Peking University First Hospital</investigator_affiliation>
    <investigator_full_name>Cui Yimin</investigator_full_name>
    <investigator_title>Director of pharmacy, M.D &amp; Ph.D</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Drug-Related Side Effects and Adverse Reactions</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/NCT03258151
org study id: 2016[1239]-2
nct id: NCT03258151
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Taxanes are one of the most active agents in the treatment of many kinds of solid tumors,
      mainly including paclitaxel and docetaxel. However, variability in toxicity and response
      remains a major problem for patients receiving taxanes. It is general that there are many
      factors for individual differences of drugs in clinical application, of which genetic factors
      accounted for more than 20%. Toxicities of docetaxel, such as myelosuppression, neurotoxicity
      or mucositis, were evaluated for possible relationship with pharmacogenetic polymorphisms in
      several candidate gene and genome-wide association studies. Due to the levels of evidence of
      those studies are low and lack of sufficient research data of Chinese, it has the important
      significance in studying individual differences of docetaxel in toxicities, through the
      pharmacogenomics research.

      The aim of this study is to evaluating the association genetic polymorphisms with
      docetaxel-based chemotherapy toxicities in chinese solid tumor patients. By detecting the
      gene polymorphism, investigators intend to study the pharmacokinetic/pharmacogenomics (PK-PG)
      correlation of docetaxel and provide scientific basis for precise medication guide for people
      to use docetaxel.
observational model: Cohort
time perspective: Other
measure: Incidence of severe hematological toxicity
time frame: At 1 year
description: The toxicity induced by docetaxel-based chemotherapy during observation time will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Patients with grade 3-4 adverse events will be considered as having severe toxicity. At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis. Hematological toxicity includes neutropenia, leukopenia, anemia and thrombocytopenia.
measure: Incidence of other severe toxicities
time frame: At 1 year
description: The other toxicities induced by docetaxel-based chemotherapy during observation time, including gastrointestinal toxicity, neurotoxicity etc., will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Toxicities with grade 3-4 will be considered as severe toxicity, except for severe neurotoxicity (grade 2-3). At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis.
measure: Genotyping
time frame: Before chemotherapy
description: Collect blood specimen, then detect genotype by next generation sequencing.
measure: The kinds of the metabolites
time frame: Pre-dose and 6 hours post-dose in the first cycle
description: Determine the metabolic profiles of docetaxel. This outcome is not applicable to patients retrospectively collected.
measure: Area under the curve [AUC]
time frame: Pre-dose and 6 hours post-dose in the first cycle
description: Determine the AUC of docetaxel and its metabolites. This outcome is not applicable to patients retrospectively collected.
arm group label: wild genotype
description: Through next generation sequencing, distinguish wild genotype of docetaxel
arm group label: mutant genotype
description: Through next generation sequencing, distinguish mutant genotype of docetaxel
intervention type: Genetic
intervention name: detection of genotype
description: detection of genotype by next generation sequencing
arm group label: mutant genotype
arm group label: wild genotype
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Peking University First Hospital
investigator full name: Cui Yimin
investigator title: Director of pharmacy, M.D & Ph.D
mesh term: Drug-Related Side Effects and Adverse Reactions