<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/NCT01672671</url>
  </required_header>
  <id_info>
    <org_study_id>TNNP 001</org_study_id>
    <secondary_id>TNNP 001</secondary_id>
    <nct_id>NCT01672671</nct_id>
  </id_info>
  <brief_title>BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy</brief_title>
  <official_title>Identification of BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Russian Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Russian Academy of Medical Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess efficacy of platinum-based neoadjuvant chemotherapy in&#xD;
      correlation with BRCA1-associated DNA repair dysfunction in patients with early triple&#xD;
      negative breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent gene expression profiling of breast cancer has identified specific subtypes with&#xD;
      clinical, biologic, and therapeutic implications. The basal-like group of tumors is&#xD;
      associated with aggressive behavior and poor prognosis, and typically do not express hormone&#xD;
      receptors or HER-2 (&quot;triple-negative&quot; phenotype). Therefore, patients with basal-like cancers&#xD;
      do not benefit from currently available targeted systemic therapy.&#xD;
&#xD;
      There is a lot of evidence about a link between basal-like breast cancer and BRCA1&#xD;
      deficiency. Many clinical characteristics and molecular features are shared by basal-like&#xD;
      breast cancers and tumors that arise in carriers of BRCA1 germline mutations.&#xD;
&#xD;
      Some studies have indicated that BRCA1 mRNA expression was lower in basal-like sporadic&#xD;
      cancers than in controls matched for age and grade. BRCA1 is rarely mutated in sporadic&#xD;
      breast cancers and, therefore, it is believed that this may be a result of epigenetic&#xD;
      mechanisms such as acquired methylation of the BRCA1 gene promoter or a dysfunction in the&#xD;
      pathways that regulate BRCA1 expression, such as overexpression of ID4. The profound&#xD;
      similarities between hereditary BRCA1-related breast tumors and basal-like tumors strongly&#xD;
      implicate a fundamental defect in the BRCA1 or associated DNA-repair pathways (p53, PTEN) in&#xD;
      sporadic basal-like tumors.&#xD;
&#xD;
      There is increasing evidence that the BRCA1-related DNA-repair defects, especially defective&#xD;
      homologous recombination, determines sensitivity to certain agents, such as platinum&#xD;
      salts-based chemotherapy. The complexity in downregulation of BRCA1 expression suggests that&#xD;
      these approaches may only be effective in the treatment of a subset of sporadic basal-like&#xD;
      cancers. Identification of specific markers for these cancers will be essential to translate&#xD;
      an understanding of defective DNA repair into targeted treatments for this poor prognosis&#xD;
      subtype.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2011</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The pathological complete response rate to neoadjuvant platinum-based chemotherapy</measure>
    <time_frame>after 8 weeks of neoadjuvant chemotherapy</time_frame>
    <description>Pathologic treatment response will be assessed in correlation with BRCA1-associated DNA repair dysfunction signature.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical responses to neadjuvant chemotherapy</measure>
    <time_frame>after 8 weeks of neoadjuvant chemotherapy</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of patients with 3/4 Grade CTC adverse events to assess toxicity and tolerability of the chemotherapy regimen</measure>
    <time_frame>after 8 weeks of neadjuvant chemotherapy</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Early Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant platinum-based chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doxorubicin, Paclitaxel, Cisplatin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin, Paclitaxel, Cisplatin</intervention_name>
    <description>Doxorubicin 25 mg/m2, IV weekly. Number of Cycles: 8 Paclitaxel 100 mg/m2, IV weekly. Number of Cycles: 8. Cisplatin 30 mg/m2, IV weekly. Number of Cycles: 8.</description>
    <arm_group_label>Neoadjuvant platinum-based chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female patients, age ≥18 years≤75;&#xD;
&#xD;
          2. Histologically confirmed invasive ER-, PR-, and HER2-negative (triple- negative)&#xD;
             adenocarcinoma of the breast;&#xD;
&#xD;
          3. Clinical stage T1-2, N0-1, M0.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment for this breast cancer&#xD;
&#xD;
          2. History of malignancy treated with curative intent within the previous 5 years with&#xD;
             the exception of skin cancer, cervical carcinoma in situ, or follicular thyroid&#xD;
             cancer. Patients with previous invasive cancers (including breast cancer) are eligible&#xD;
             if the treatment was completed more than 5 years prior to initiating current study&#xD;
             treatment, and there is no evidence of recurrent disease&#xD;
&#xD;
          3. Pregnancy or breast-feeding&#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>Russian Cancer Research Center named after N.N.Blokhin RAMS</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <link>
    <url>http://www.ncbi.nlm.nih.gov/pubmed</url>
    <description>Breast Cancer, Neoadjuvant Chemotherapy</description>
  </link>
  <link>
    <url>http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp</url>
    <description>Doxorubicin, Paclitaxel, Cisplatin</description>
  </link>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>August 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <last_update_submitted>November 1, 2015</last_update_submitted>
  <last_update_submitted_qc>November 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Russian Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Mona Frolova</investigator_full_name>
    <investigator_title>Research Associate of Department of Clinical Pharmacology and Chemotherapy</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Doxorubicin</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/NCT01672671
org study id: TNNP 001
secondary id: TNNP 001
nct id: NCT01672671
lead sponsor: 
has dmc: No
The purpose of this study is to assess efficacy of platinum-based neoadjuvant chemotherapy in
      correlation with BRCA1-associated DNA repair dysfunction in patients with early triple
      negative breast cancer.
Recent gene expression profiling of breast cancer has identified specific subtypes with
      clinical, biologic, and therapeutic implications. The basal-like group of tumors is
      associated with aggressive behavior and poor prognosis, and typically do not express hormone
      receptors or HER-2 ("triple-negative" phenotype). Therefore, patients with basal-like cancers
      do not benefit from currently available targeted systemic therapy.

      There is a lot of evidence about a link between basal-like breast cancer and BRCA1
      deficiency. Many clinical characteristics and molecular features are shared by basal-like
      breast cancers and tumors that arise in carriers of BRCA1 germline mutations.

      Some studies have indicated that BRCA1 mRNA expression was lower in basal-like sporadic
      cancers than in controls matched for age and grade. BRCA1 is rarely mutated in sporadic
      breast cancers and, therefore, it is believed that this may be a result of epigenetic
      mechanisms such as acquired methylation of the BRCA1 gene promoter or a dysfunction in the
      pathways that regulate BRCA1 expression, such as overexpression of ID4. The profound
      similarities between hereditary BRCA1-related breast tumors and basal-like tumors strongly
      implicate a fundamental defect in the BRCA1 or associated DNA-repair pathways (p53, PTEN) in
      sporadic basal-like tumors.

      There is increasing evidence that the BRCA1-related DNA-repair defects, especially defective
      homologous recombination, determines sensitivity to certain agents, such as platinum
      salts-based chemotherapy. The complexity in downregulation of BRCA1 expression suggests that
      these approaches may only be effective in the treatment of a subset of sporadic basal-like
      cancers. Identification of specific markers for these cancers will be essential to translate
      an understanding of defective DNA repair into targeted treatments for this poor prognosis
      subtype.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The pathological complete response rate to neoadjuvant platinum-based chemotherapy
time frame: after 8 weeks of neoadjuvant chemotherapy
description: Pathologic treatment response will be assessed in correlation with BRCA1-associated DNA repair dysfunction signature.
measure: Disease-free survival
time frame: 3 years
measure: Clinical responses to neadjuvant chemotherapy
time frame: after 8 weeks of neoadjuvant chemotherapy
measure: Number of patients with 3/4 Grade CTC adverse events to assess toxicity and tolerability of the chemotherapy regimen
time frame: after 8 weeks of neadjuvant chemotherapy
arm group label: Neoadjuvant platinum-based chemotherapy
arm group type: Experimental
description: Doxorubicin, Paclitaxel, Cisplatin
intervention type: Drug
intervention name: Doxorubicin, Paclitaxel, Cisplatin
description: Doxorubicin 25 mg/m2, IV weekly. Number of Cycles: 8 Paclitaxel 100 mg/m2, IV weekly. Number of Cycles: 8. Cisplatin 30 mg/m2, IV weekly. Number of Cycles: 8.
arm group label: Neoadjuvant platinum-based chemotherapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Russian Federation
url: http://www.ncbi.nlm.nih.gov/pubmed
description: Breast Cancer, Neoadjuvant Chemotherapy
url: http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp
description: Doxorubicin, Paclitaxel, Cisplatin
responsible party type: Principal Investigator
investigator affiliation: Russian Academy of Medical Sciences
investigator full name: Mona Frolova
investigator title: Research Associate of Department of Clinical Pharmacology and Chemotherapy
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Paclitaxel
mesh term: Doxorubicin