xml: <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/NCT05983107</url>
    </required_header>
    <id_info>
      <org_study_id>NCC4048</org_study_id>
      <nct_id>NCT05983107</nct_id>
    </id_info>
    <brief_title>Chidamide/Everolimus for PIK3CA Wild-type/Mutant HR+/HER2- Advanced Breast Cancer</brief_title>
    <official_title>A Prospective Cohort, Open, Phase II Clinical Study of Chidamide/Everolimus Combined With Endocrine Therapy for PIK3CA Wild-type/Mutant Hormone Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative Advanced Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</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>
        To explore the efficacy and safety of chidamide combined with endocrine in&#xD;
        phosphoinositide-3-kinase,catalytic,alpha gene(PI3KCA) wild type hormone receptor&#xD;
        positive(HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast&#xD;
        cancer patients and to explore the efficacy and safety of Everolimus combined with endocrine&#xD;
        therapy in patients with PI3KCA Mutant HR+/HER2- advanced breast cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is an open, multi center, prospective cohort, and Phase II exploratory research.&#xD;
        According to the PIK3CA gene mutation status of patients, the study is divided into two&#xD;
        cohorts. The PIK3CA Mutant uses everolimus combined with endocrine therapy as the cohort A,&#xD;
        and the PIK3CA wild type uses chidamide combined with endocrine therapy as the cohort B,&#xD;
        until the disease progresses or the toxicity is intolerable. According to the judgment of the&#xD;
        researchers, whether to enter the second stage of cross design, Queue A was cross&#xD;
        administered with chidamide in combination with endocrine therapy. Cohort B cross used&#xD;
        everolimus combined with endocrine until the disease progressed or the toxicity was&#xD;
        intolerable.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 20, 2023</start_date>
    <completion_date type="Anticipated">July 15, 2027</completion_date>
    <primary_completion_date type="Anticipated">July 15, 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>First stage progression free survival (PFS1)</measure>
      <time_frame>2 years</time_frame>
      <description>First stage progression free survival (PFS1)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>2 years</time_frame>
      <description>Overall survival (OS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>objective response rate (ORR)</measure>
      <time_frame>2 years</time_frame>
      <description>objective response rate (ORR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>disease control rate (DCR)</measure>
      <time_frame>2 years</time_frame>
      <description>disease control rate (DCR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>clinical benefit rate (CBR)</measure>
      <time_frame>2 years</time_frame>
      <description>clinical benefit rate (CBR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>time to chemotherapy</measure>
      <time_frame>Through study completion，an average of 1 year</time_frame>
      <description>time to chemotherapy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>chemotherapy free survival</measure>
      <time_frame>Through study completion，an average of 1 year</time_frame>
      <description>chemotherapy free survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>patient reported outcome indicators (PRO)</measure>
      <time_frame>Through study completion，an average of 1 year</time_frame>
      <description>National Cancer Center of China-Breast Cancer-A 1.0 (NCC-BC-A 1.0) during the study was used to assess the quality of life；The minimum to maximum values: 0 , 100 Meaning: the higher scores mean a better outcome.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">102</enrollment>
    <condition>HR+/HER2- Advanced Breast Cancer</condition>
    <condition>Targeted Therapy</condition>
    <arm_group>
      <arm_group_label>cohort 1 PIK3CA Mutant</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Everolimus combined with endocrine therapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>cohort 2 PIK3CA wild type</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>chidamide combined with endocrine therapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Everolimus</intervention_name>
      <description>Everolimus combined with endocrine therapy（tamoxifen, letrozole, anastrozole, exemestane, fulvestrant, etc.Goserelin, leuprolide, premenopausal patients only, selected at the discretion of the investigator）</description>
      <arm_group_label>cohort 1 PIK3CA Mutant</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Chidamide</intervention_name>
      <description>Chidamide combined with endocrine therapy（tamoxifen, letrozole, anastrozole, exemestane, fulvestrant, etc.goserelin, leuprolide, premenopausal patients only, selected at the discretion of the investigator）</description>
      <arm_group_label>cohort 2 PIK3CA wild type</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Endocrine therapy</intervention_name>
      <description>Tamoxifen, letrozole, anastrozole, exemestane, fulvestrant, etc, selected at the discretion of the investigator.</description>
      <arm_group_label>cohort 1 PIK3CA Mutant</arm_group_label>
      <arm_group_label>cohort 2 PIK3CA wild type</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ovarian function suppression(OFS)</intervention_name>
      <description>Goserelin, leuprolide, premenopausal patients only, selected at the discretion of the investigator.</description>
      <arm_group_label>cohort 1 PIK3CA Mutant</arm_group_label>
      <arm_group_label>cohort 2 PIK3CA wild type</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  The age at the time of signing the informed consent form is ≥ 18 years old and ≤ 75&#xD;
               years old, for menopausal/premenopausal women (premenopausal women need to receive&#xD;
               ovarian function suppression treatment at the same time).&#xD;
  &#xD;
            -  Breast cancer patients with HR positive (ER expression ≥ 10%, PR positive or negative)&#xD;
               and HER2 negative (Immunohistochemical(IHC)0,1+; 2+, Fluorescence in situ&#xD;
               hybridization(FISH) not expanded) confirmed by histology.&#xD;
  &#xD;
            -  Histologically confirmed locally advanced breast cancer (no radical local treatment)&#xD;
               or recurrent and metastatic breast cancer.&#xD;
  &#xD;
            -  The patients who had previously progressed after the treatment of first-line or&#xD;
               second-line cyclin-dependent kinases 4 and 6 inhibitors（CDK4/6 inhibitors）of endocrine&#xD;
               and whose chemotherapy was ≤ second-line (relapse during the period of new&#xD;
               adjuvant/adjuvant treatment or within 12 months after the end of treatment was&#xD;
               regarded as first-line chemotherapy), the PIK3CA gene mutation detection was performed&#xD;
               a. PIK3CA Mutant subjects were enrolled in queue A; b. PIK3CA wild-type subjects were&#xD;
               included in queue B.&#xD;
  &#xD;
            -  At least one measurable primary lesion (according to RECIST v1.1 standard) before&#xD;
               enrollment.&#xD;
  &#xD;
            -  The Eastern Oncology Collaborative Group (ECOG) physical fitness score is 0-2.&#xD;
  &#xD;
            -  The toxic and side effects caused by previous anti-tumor therapy were relieved to 0-1&#xD;
               levels before the screening period (judged according to The NCI Common Terminology&#xD;
               Criteria for Adverse Events version5.0 (NCICTCAE5.0); except for toxicity that&#xD;
               researchers believe does not pose a safety risk to the subjects due to hair loss).&#xD;
  &#xD;
            -  The functional level of organs must meet the following requirements: 1) Blood routine:&#xD;
  &#xD;
          Absolute neutrophil count(ANC)≥1.5 × 109/L (growth factor not used within 14 days);&#xD;
          Platelet(PLT) ≥100 × 109/L (no corrective treatment used within 7 days); Hb ≥ 100 g/L&#xD;
          (without corrective treatment within 7 days); 2) Blood biochemistry: Total bilirubin(TBIL)&#xD;
          ≤1.5 × upper limits of normal(ULN); Glutamine aminotransferase(ALT),Glutamic&#xD;
          transaminase(AST)≤3 × ULN; Glutamine transpeptidase(GGT) ≤2.5 × ULN; If there is liver&#xD;
          metastasis, then ALT and/or AST ≤ 5 × ULN; Glutamine transpeptidase GGT ≤5 × ULN; Urea,&#xD;
          Blood urea nitrogen (BUN), creatinine (Cr) ≤1.5 × ULN; 3) Cardiac ultrasound: Left&#xD;
          ventricular ejection fraction（LVEF）≥ 50%; 4) 12 lead ECG: QT interval (QTcF) corrected by&#xD;
          Fridericia method, male&lt;450ms, female.&#xD;
  &#xD;
            -  Expected survival time ≥ 3 months.&#xD;
  &#xD;
            -  Voluntarily participate in this clinical trial and sign a written informed consent&#xD;
               form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Those who have received any mammalian target of rapamycin（mTOR） and histone&#xD;
               deacetylase（HDAC） inhibitors at any time in the past.&#xD;
  &#xD;
            -  Received chemotherapy, Targeted therapy, immunotherapy, interventional therapy or&#xD;
               other systematic anti-tumor treatment within 4 weeks before the first administration&#xD;
               of the study drug, or received radiotherapy within 3 weeks Note: Nitroso urea or&#xD;
               Mitomycin C is within 6 weeks before the first use of the study drug, oral&#xD;
               fluorouracil and small molecule targeted drugs are within 2 weeks before the first use&#xD;
               of the study drug or within 5 half lives of the drug (whichever is longer),&#xD;
               Traditional Chinese medicine with anti-tumor indications should be used within 2 weeks&#xD;
               before the first use of the study drug.&#xD;
  &#xD;
            -  Subjects who have undergone major surgical procedures or obvious trauma within 4 weeks&#xD;
               prior to enrollment, or are expected to undergo major surgical treatment.&#xD;
  &#xD;
            -  Subjects with brain or subdural metastasis are excluded. Unless its stability has been&#xD;
               maintained for at least 4 weeks or Asymptomatic brain metastasis can be included in&#xD;
               the group.&#xD;
  &#xD;
            -  According to the investigator's judgment, there are concomitant diseases (such as&#xD;
               severe hypertension, Thyroid disease, hyperlipidemia, active infection, etc.) that&#xD;
               seriously endanger the patient's safety or affect the patient's completion of the&#xD;
               study.&#xD;
  &#xD;
            -  Patients with poor control of diabetes shall be determined by the researcher.&#xD;
  &#xD;
            -  Clinically obvious gastrointestinal abnormalities that may affect drug intake,&#xD;
               transport or absorption (such as inability to swallow, chronic diarrhea, Bowel&#xD;
               obstruction, etc.).&#xD;
  &#xD;
            -  Severe cardiovascular injury (greater than a history of congestive heart failure at&#xD;
               New York Heart Association(NYHA) level II, unstable angina or myocardial infarction&#xD;
               within the past 6 months, or severe arrhythmia.&#xD;
  &#xD;
            -  Subjects have active hepatitis (hepatitis B reference: HBsAg positive and hepatitis B&#xD;
               virus(HBV) DNA ≥ 500 international unit(IU)/ml; hepatitis C reference: hepatitis C&#xD;
               virus(HCV) antibody positive and HCV copy number&gt;upper limit of normal value);&#xD;
               Subjects who are known to be positive for human immunodeficiency virus (HIV).&#xD;
  &#xD;
            -  Female patients during pregnancy and lactation, female patients with Fertility and&#xD;
               positive baseline Pregnancy test, or those of childbearing age who are unwilling to&#xD;
               take effective contraceptive measures during the whole test period and within 90 days&#xD;
               after the last administration of the study drug.&#xD;
  &#xD;
            -  Have a clear history of neurological or mental disorders, including epilepsy or&#xD;
               dementia, in the past.&#xD;
  &#xD;
            -  Any medical condition in which the researcher believes that the subject is not&#xD;
               suitable for entry into the study.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100021</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Fei Ma</last_name>
        <phone>010-87788120</phone>
        <email>drmafei@126.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
      <investigator_full_name>Ma Fei，MD</investigator_full_name>
      <investigator_title>Deputy Director of the Department of Medical Oncology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Everolimus</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05983107
  org study id: NCC4048
  nct id: NCT05983107
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  To explore the efficacy and safety of chidamide combined with endocrine in
        phosphoinositide-3-kinase,catalytic,alpha gene(PI3KCA) wild type hormone receptor
        positive(HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast
        cancer patients and to explore the efficacy and safety of Everolimus combined with endocrine
        therapy in patients with PI3KCA Mutant HR+/HER2- advanced breast cancer.
  This study is an open, multi center, prospective cohort, and Phase II exploratory research.
        According to the PIK3CA gene mutation status of patients, the study is divided into two
        cohorts. The PIK3CA Mutant uses everolimus combined with endocrine therapy as the cohort A,
        and the PIK3CA wild type uses chidamide combined with endocrine therapy as the cohort B,
        until the disease progresses or the toxicity is intolerable. According to the judgment of the
        researchers, whether to enter the second stage of cross design, Queue A was cross
        administered with chidamide in combination with endocrine therapy. Cohort B cross used
        everolimus combined with endocrine until the disease progressed or the toxicity was
        intolerable.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: First stage progression free survival (PFS1)
  time frame: 2 years
  description: First stage progression free survival (PFS1)
  measure: Overall survival (OS)
  time frame: 2 years
  description: Overall survival (OS)
  measure: objective response rate (ORR)
  time frame: 2 years
  description: objective response rate (ORR)
  measure: disease control rate (DCR)
  time frame: 2 years
  description: disease control rate (DCR)
  measure: clinical benefit rate (CBR)
  time frame: 2 years
  description: clinical benefit rate (CBR)
  measure: time to chemotherapy
  time frame: Through study completion，an average of 1 year
  description: time to chemotherapy
  measure: chemotherapy free survival
  time frame: Through study completion，an average of 1 year
  description: chemotherapy free survival
  measure: patient reported outcome indicators (PRO)
  time frame: Through study completion，an average of 1 year
  description: National Cancer Center of China-Breast Cancer-A 1.0 (NCC-BC-A 1.0) during the study was used to assess the quality of life；The minimum to maximum values: 0 , 100 Meaning: the higher scores mean a better outcome.
  arm group label: cohort 1 PIK3CA Mutant
  arm group type: Experimental
  description: Everolimus combined with endocrine therapy
  arm group label: cohort 2 PIK3CA wild type
  arm group type: Experimental
  description: chidamide combined with endocrine therapy
  intervention type: Drug
  intervention name: Everolimus
  description: Everolimus combined with endocrine therapy（tamoxifen, letrozole, anastrozole, exemestane, fulvestrant, etc.Goserelin, leuprolide, premenopausal patients only, selected at the discretion of the investigator）
  arm group label: cohort 1 PIK3CA Mutant
  intervention type: Drug
  intervention name: Chidamide
  description: Chidamide combined with endocrine therapy（tamoxifen, letrozole, anastrozole, exemestane, fulvestrant, etc.goserelin, leuprolide, premenopausal patients only, selected at the discretion of the investigator）
  arm group label: cohort 2 PIK3CA wild type
  intervention type: Drug
  intervention name: Endocrine therapy
  description: Tamoxifen, letrozole, anastrozole, exemestane, fulvestrant, etc, selected at the discretion of the investigator.
  arm group label: cohort 1 PIK3CA Mutant
  arm group label: cohort 2 PIK3CA wild type
  intervention type: Drug
  intervention name: Ovarian function suppression(OFS)
  description: Goserelin, leuprolide, premenopausal patients only, selected at the discretion of the investigator.
  arm group label: cohort 1 PIK3CA Mutant
  arm group label: cohort 2 PIK3CA wild type
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  investigator full name: Ma Fei，MD
  investigator title: Deputy Director of the Department of Medical Oncology
  mesh term: Breast Neoplasms
  mesh term: Everolimus