<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/NCT02204306</url>
  </required_header>
  <id_info>
    <org_study_id>1000 Talents-CSU-GC</org_study_id>
    <secondary_id>1000 Plan</secondary_id>
    <nct_id>NCT02204306</nct_id>
  </id_info>
  <brief_title>Genotype Guided Chemotherapy in Gastric Cancer Patients</brief_title>
  <official_title>TSER Genotype Guided Chemotherapy in Metastatic Gastric Cancer Patients: A Phase II Study in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central South University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Central South University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In gastric cancer patients treated with 5-FU and cisplatin, higher tumor TS levels were&#xD;
      associated with a less favorable response (29% vs. 68%; p=0.024). Similarly, in a study in&#xD;
      which patients were treated with high dose 5-FU, patients with high TS expression had a&#xD;
      response rate of only 12.5%. Conversely a response rate of 92.9% was observed in patients&#xD;
      with low tumor TS expression. A longer but not statistically significant survival advantage&#xD;
      was observed in patients with the TSER*2 allele compared with the TSER*3/*3 patients.&#xD;
      Additionally, a review by Patel et al. identified approximately 20 gastric cancer studies&#xD;
      that have found a positive association between TSER genotype and clinical response (in either&#xD;
      direction). Therefore, the primary goal of this proposal is to prospectively genotype&#xD;
      patients, select patients with &quot;good risk&quot; TSER genotypes (TSER*2*/*2 or *2/*3) and treat&#xD;
      them with a standard 5-FU containing regimen (FOLFOX) in order to improve clinical outcomes,&#xD;
      while randomize patients with the &quot;poor risk&quot; TSER genotype (*3/*3) to either the standard&#xD;
      5-FU containing regimen or another non-5-FU-based regimen (docetaxel/cisplatin).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</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>disease control rate</measure>
    <time_frame>6 and 12 weeks after the first chemotherapy</time_frame>
    <description>Determine whether the disease control rate (DCR) at 6 and 12 weeks in TSER*3/*3 patients with metastatic gastric cancer will be increased by using a non fluoropyrimidine containing regimen compared to fluoropyrimidine-containing regimens.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>time to progression</measure>
    <time_frame>2 years maximum</time_frame>
    <description>TTP is defined in this study as: &quot;The length of time from the date of the start of treatment for gastric cancer until the disease starts to get worse or spread to other parts of the body.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>median overall survival</measure>
    <time_frame>2 years maximum</time_frame>
    <description>median overall survival is defined in this study as: &quot;The length of time from the start of treatment for a disease that half of the patients in a group of patients diagnosed with the disease are still alive.&quot;</description>
  </secondary_outcome>
  <other_outcome>
    <measure>drug toxicities</measure>
    <time_frame>2 years maximum</time_frame>
    <description>Drug toxicities will be recorded and evaluated by NCI CTCAE v3.0.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">330</enrollment>
  <condition>Metastatic Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>TSER *2/*2 *2/*3</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients with TSER *2/*2 *2/*3 genotypes will be assigned to this group and receive standard chemotherapy contains fluorouracil. (FOLFOX 6/XELOX/SOX)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TSER*3/*3 (fluorouracil)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients with TSER*3/*3 genotype will be randomly assigned to fluorouracil group (FOLFOX 6/XELOX/SOX) or non-fluorouracil group (DC or DO).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TSER*3/*3 (non-fluorouracil)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients with TSER*3/*3 genotype will be randomly assigned to fluorouracil group (FOLFOX 6/XELOX/SOX) or non-fluorouracil group (DC or DO).</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>TSER</intervention_name>
    <description>TS gene will be genotyped for each patients prior to chemotherapy. Patients will be assigned to different arms according to specific TSER genotype.</description>
    <arm_group_label>TSER *2/*2 *2/*3</arm_group_label>
    <arm_group_label>TSER*3/*3 (fluorouracil)</arm_group_label>
    <arm_group_label>TSER*3/*3 (non-fluorouracil)</arm_group_label>
    <other_name>TSER genotypes: *2/*2 *2/*3 *3/*3</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have histologically or cytologically confirmed metastatic adenocarcinoma&#xD;
             of the stomach.&#xD;
&#xD;
          2. Patients must have measurable disease, defined as at least one lesion that can be&#xD;
             accurately measured in at least one dimension (longest diameter to be recorded) as &gt;20&#xD;
             mm with conventional techniques or as &gt;10 mm with spiral CT scan. See section 9.2 for&#xD;
             the evaluation of measurable disease.&#xD;
&#xD;
          3. No prior therapy for metastatic disease. Prior neo-adjuvant or adjuvant therapy is&#xD;
             permitted if the disease free interval has been longer than 12 months.&#xD;
&#xD;
          4. Age between 18 and 70 years. Because no dosing or adverse event data are currently&#xD;
             available on the use of these regimens in patients &lt;18 years of age, children are&#xD;
             excluded from this study.&#xD;
&#xD;
          5. Life expectancy of greater than 3 months.&#xD;
&#xD;
          6. ECOG performance status &lt; 2 (Karnofsky &gt;60%; see Appendix A).&#xD;
&#xD;
          7. Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Leukocytes &gt;3,000/microliter&#xD;
&#xD;
               -  Absolute neutrophil count &gt;1,500/microliter&#xD;
&#xD;
               -  Platelets &gt;100,000/microliter&#xD;
&#xD;
               -  Total bilirubin &lt; 1.5 x ULN&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) &lt;2.5 x ULN if not liver metastases &lt; 5 x ULN if known liver&#xD;
                  metastases&#xD;
&#xD;
               -  Creatinine clearance &lt;1.5 x ULN&#xD;
&#xD;
          8. Not pregnant. Not breast feeding. If the patient or partner is of childbearing&#xD;
             potential, the couple will use adequate birth control in accordance with local IRB&#xD;
             policies:&#xD;
&#xD;
             For woman of childbearing potential:&#xD;
&#xD;
             Patient must have negative blood pregnancy test. If sexually active, woman must either&#xD;
             be post-menopausal (over age 50 and have not had a menstrual period for one year or&#xD;
             more, or blood FSH level in the post-menopausal range) OR agree to use appropriate&#xD;
             contraceptive measures for the duration of the study and for 21 days after stopping&#xD;
             study treatment. The only birth control methods for women that are acceptable for this&#xD;
             study are: (1) surgical sterilization (previous removal of the uterus or both ovaries&#xD;
             or a tubal ligation) OR (2) an intrauterine device (IUD), (3) double barrier methods,&#xD;
             (4) oral contraceptives.&#xD;
&#xD;
             For men:&#xD;
&#xD;
             Medically acceptable contraceptives include: (1) surgical sterilization, or (2) a&#xD;
             condom used with a spermicide. If the female partner becomes pregnant while patient is&#xD;
             on treatment or within 21 days after stopping treatment, the study physician must be&#xD;
             informed.&#xD;
&#xD;
          9. Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients may not be receiving any other chemotherapy agents.&#xD;
&#xD;
          2. Patients with known active brain metastases. Patients with treated brain metastases&#xD;
             are permitted if stable off steroids for at least 30 days. A screening head CT/MRI is&#xD;
             not required in asymptomatic patients for this protocol.&#xD;
&#xD;
          3. History of allergic reactions to 5-FU, oxaliplatin, docetaxel, or cisplatin.&#xD;
&#xD;
          4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          5. Patients with immune deficiency are at increased risk of lethal infections when&#xD;
             treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving&#xD;
             combination anti-retroviral therapy are excluded from the study because of possible&#xD;
             pharmacokinetic interactions with the chemotherapies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Institute of Clinical Pharmacology</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410005</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>November 15, 2019</last_update_submitted>
  <last_update_submitted_qc>November 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Central South University</investigator_affiliation>
    <investigator_full_name>Yijing He</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</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/NCT02204306
org study id: 1000 Talents-CSU-GC
secondary id: 1000 Plan
nct id: NCT02204306
lead sponsor: 
has dmc: Yes
In gastric cancer patients treated with 5-FU and cisplatin, higher tumor TS levels were
      associated with a less favorable response (29% vs. 68%; p=0.024). Similarly, in a study in
      which patients were treated with high dose 5-FU, patients with high TS expression had a
      response rate of only 12.5%. Conversely a response rate of 92.9% was observed in patients
      with low tumor TS expression. A longer but not statistically significant survival advantage
      was observed in patients with the TSER*2 allele compared with the TSER*3/*3 patients.
      Additionally, a review by Patel et al. identified approximately 20 gastric cancer studies
      that have found a positive association between TSER genotype and clinical response (in either
      direction). Therefore, the primary goal of this proposal is to prospectively genotype
      patients, select patients with "good risk" TSER genotypes (TSER*2*/*2 or *2/*3) and treat
      them with a standard 5-FU containing regimen (FOLFOX) in order to improve clinical outcomes,
      while randomize patients with the "poor risk" TSER genotype (*3/*3) to either the standard
      5-FU containing regimen or another non-5-FU-based regimen (docetaxel/cisplatin).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: disease control rate
time frame: 6 and 12 weeks after the first chemotherapy
description: Determine whether the disease control rate (DCR) at 6 and 12 weeks in TSER*3/*3 patients with metastatic gastric cancer will be increased by using a non fluoropyrimidine containing regimen compared to fluoropyrimidine-containing regimens.
measure: time to progression
time frame: 2 years maximum
description: TTP is defined in this study as: "The length of time from the date of the start of treatment for gastric cancer until the disease starts to get worse or spread to other parts of the body."
measure: median overall survival
time frame: 2 years maximum
description: median overall survival is defined in this study as: "The length of time from the start of treatment for a disease that half of the patients in a group of patients diagnosed with the disease are still alive."
measure: drug toxicities
time frame: 2 years maximum
description: Drug toxicities will be recorded and evaluated by NCI CTCAE v3.0.
arm group label: TSER *2/*2 *2/*3
arm group type: Other
description: Patients with TSER *2/*2 *2/*3 genotypes will be assigned to this group and receive standard chemotherapy contains fluorouracil. (FOLFOX 6/XELOX/SOX)
arm group label: TSER*3/*3 (fluorouracil)
arm group type: Other
description: Patients with TSER*3/*3 genotype will be randomly assigned to fluorouracil group (FOLFOX 6/XELOX/SOX) or non-fluorouracil group (DC or DO).
arm group label: TSER*3/*3 (non-fluorouracil)
arm group type: Other
description: Patients with TSER*3/*3 genotype will be randomly assigned to fluorouracil group (FOLFOX 6/XELOX/SOX) or non-fluorouracil group (DC or DO).
intervention type: Genetic
intervention name: TSER
description: TS gene will be genotyped for each patients prior to chemotherapy. Patients will be assigned to different arms according to specific TSER genotype.
arm group label: TSER *2/*2 *2/*3
arm group label: TSER*3/*3 (fluorouracil)
arm group label: TSER*3/*3 (non-fluorouracil)
other name: TSER genotypes: *2/*2 *2/*3 *3/*3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Central South University
investigator full name: Yijing He
investigator title: Associate Professor
mesh term: Stomach Neoplasms