<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/NCT03797482</url>
  </required_header>
  <id_info>
    <org_study_id>Protocol 254</org_study_id>
    <nct_id>NCT03797482</nct_id>
  </id_info>
  <brief_title>A Prospective Evaluation of the Peri-operative Hypoxia in Breast Cancer</brief_title>
  <acronym>Hypoxia</acronym>
  <official_title>A Prospective Evaluation of the Peri-operative Hypoxia in Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tata Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tata Memorial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      To understand the effects induced by acute hypoxia that sets in during surgery in breast&#xD;
      cancer. To study this, clinical samples (Tumor biopsies) will be obtained during the surgery&#xD;
      after partial devascularisation (sample B) and stored for future genomic and proteonomic&#xD;
      evaluations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Three tumor samples will be obtained after the patient is under anaesthesia,&#xD;
&#xD;
        1. Prior to starting surgery (Sample A)&#xD;
&#xD;
        2. The middle intra-operative sample, which will be collected when half the tumour has been&#xD;
           devascularized (i.e., somewhere midway during the surgery). (Sample B)&#xD;
&#xD;
        3. A third post excision (anoxic sample C). These tumour tissue samples will be stored as&#xD;
           snap frozen, in RNA later and as paraffin sections.&#xD;
&#xD;
      To understand the effects induced by acute hypoxia that sets in during surgery in breast&#xD;
      cancer. To study this, clinical samples (Tumor biopsies) will be obtained during and stored&#xD;
      for future genomic and proteonomic evaluations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 27, 2017</start_date>
  <completion_date type="Anticipated">November 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Gene expression changes</measure>
    <time_frame>The study aims to evaluate gene expression changes during surgical resection, which lasts for 30-90 minutes on an average. Thus, we have not planned a clinical follow-up or collection of data for the patients post sampling during surgical resection.</time_frame>
    <description>The primary outcome measured will be gene expression changes during surgical resection. Messenger ribonucleic acid (mRNA) transcripts will be quantitated and their levels evaluated during different time-points of surgical resection, using high throughput omics technologies (Next generation sequencing, nanostring ncounter, qRT-PCR array).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunohistochemistry for other markers</measure>
    <time_frame>The study aims to evaluate gene expression changes during surgical resection, which lasts for 30-90 minutes on an average. Thus, we have not planned a clinical follow-up or collection of data for the patients post sampling during surgical resection.</time_frame>
    <description>The secondary outcome measured will be protein expression changes during surgical resection. Protein levels will be quantitated, and their levels evaluated, during different time-points of surgical resection. Transcripts found to be de-regulated or changed at different time-points of surgical resection will be evaluated using IHC at protein level. We will also use high throughput omics technologies (SILAC, ITRAQ) for characterising these changes at protein levels.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Breast Cancer Female</condition>
  <arm_group>
    <arm_group_label>Intra-operative tumour tissue biopsies</arm_group_label>
    <description>Intra-operative tumour tissue biopsies will be collected for all patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intra-operative Tumor Tissue Biopsy</intervention_name>
    <description>The changing pattern of gene expression during surgery has never been studied. This could be an effect of acute hypoxia that sets in the tumour during surgery or could be a surgical response. To study these changes happening in the tumour during surgery, we are taking serial biopsies during surgery, one at the beginning, one midway during surgery and one at the end of surgery. These samples will be snap frozen and stored at -80 deg celsius in biorepository for future analysis.</description>
    <arm_group_label>Intra-operative tumour tissue biopsies</arm_group_label>
    <other_name>Breast cancer surgery</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Breast cancer tumor tissue&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Women diagnosed with breast cancer at outpatient clinic&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinically diagnosis of breast cancer (by FNAC or Biopsy)&#xD;
&#xD;
          2. Not received any chemotherapy or surgical intervention except core biopsy.&#xD;
&#xD;
          3. Planed for Breast cancer surgery&#xD;
&#xD;
          4. Willing to give consent for the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinically diagnosis of Metastatic breast cancer&#xD;
&#xD;
          2. Received any anticancer therapy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Women diagnosed with breast cancer, undergoing surgery upfront</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rajendra Badwe</last_name>
    <role>Principal Investigator</role>
    <affiliation>Director, tata Memorial Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shalaka Joshi, MS, MCh</last_name>
    <phone>9869089803</phone>
    <phone_ext>4265</phone_ext>
    <email>drjoshishalaka@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rohini A Hawaldar</last_name>
    <phone>09820432613</phone>
    <email>rwhawaldar@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Tata Memorial Center</name>
      <address>
        <city>Mumbai</city>
        <state>Maharashtra</state>
        <zip>400012</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shalaka Joshi, MS, MCh</last_name>
      <phone>22241608601</phone>
      <phone_ext>4265</phone_ext>
      <email>drjoshishalaka@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Rohini A Hawaldar, BSc</last_name>
      <phone>09820432613</phone>
      <email>rwhawaldar@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <reference>
    <citation>Semenza GL. Cancer-stromal cell interactions mediated by hypoxia-inducible factors promote angiogenesis, lymphangiogenesis, and metastasis. Oncogene. 2013 Aug 29;32(35):4057-63. doi: 10.1038/onc.2012.578. Epub 2012 Dec 10.</citation>
    <PMID>23222717</PMID>
  </reference>
  <reference>
    <citation>Hockel M, Vaupel P. Biological consequences of tumor hypoxia. Semin Oncol. 2001 Apr;28(2 Suppl 8):36-41.</citation>
    <PMID>11395851</PMID>
  </reference>
  <reference>
    <citation>Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer. 2013 Aug 2;12:86. doi: 10.1186/1476-4598-12-86.</citation>
    <PMID>23915189</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 28, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>April 11, 2023</last_update_submitted>
  <last_update_submitted_qc>April 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tata Memorial Centre</investigator_affiliation>
    <investigator_full_name>Dr Rajendra A. Badwe</investigator_full_name>
    <investigator_title>Director, Tata Memorial Centre and Professor, Department of Surgical Oncology</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>Hypoxia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03797482
org study id: Protocol 254
nct id: NCT03797482
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To understand the effects induced by acute hypoxia that sets in during surgery in breast
      cancer. To study this, clinical samples (Tumor biopsies) will be obtained during the surgery
      after partial devascularisation (sample B) and stored for future genomic and proteonomic
      evaluations.
Three tumor samples will be obtained after the patient is under anaesthesia,

        1. Prior to starting surgery (Sample A)

        2. The middle intra-operative sample, which will be collected when half the tumour has been
           devascularized (i.e., somewhere midway during the surgery). (Sample B)

        3. A third post excision (anoxic sample C). These tumour tissue samples will be stored as
           snap frozen, in RNA later and as paraffin sections.

      To understand the effects induced by acute hypoxia that sets in during surgery in breast
      cancer. To study this, clinical samples (Tumor biopsies) will be obtained during and stored
      for future genomic and proteonomic evaluations.
observational model: Other
time perspective: Prospective
measure: Gene expression changes
time frame: The study aims to evaluate gene expression changes during surgical resection, which lasts for 30-90 minutes on an average. Thus, we have not planned a clinical follow-up or collection of data for the patients post sampling during surgical resection.
description: The primary outcome measured will be gene expression changes during surgical resection. Messenger ribonucleic acid (mRNA) transcripts will be quantitated and their levels evaluated during different time-points of surgical resection, using high throughput omics technologies (Next generation sequencing, nanostring ncounter, qRT-PCR array).
measure: Immunohistochemistry for other markers
time frame: The study aims to evaluate gene expression changes during surgical resection, which lasts for 30-90 minutes on an average. Thus, we have not planned a clinical follow-up or collection of data for the patients post sampling during surgical resection.
description: The secondary outcome measured will be protein expression changes during surgical resection. Protein levels will be quantitated, and their levels evaluated, during different time-points of surgical resection. Transcripts found to be de-regulated or changed at different time-points of surgical resection will be evaluated using IHC at protein level. We will also use high throughput omics technologies (SILAC, ITRAQ) for characterising these changes at protein levels.
arm group label: Intra-operative tumour tissue biopsies
description: Intra-operative tumour tissue biopsies will be collected for all patients
intervention type: Procedure
intervention name: Intra-operative Tumor Tissue Biopsy
description: The changing pattern of gene expression during surgery has never been studied. This could be an effect of acute hypoxia that sets in the tumour during surgery or could be a surgical response. To study these changes happening in the tumour during surgery, we are taking serial biopsies during surgery, one at the beginning, one midway during surgery and one at the end of surgery. These samples will be snap frozen and stored at -80 deg celsius in biorepository for future analysis.
arm group label: Intra-operative tumour tissue biopsies
other name: Breast cancer surgery
Breast cancer tumor tissue
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: Women diagnosed with breast cancer, undergoing surgery upfront
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rajendra Badwe
role: Principal Investigator
affiliation: Director, tata Memorial Centre
last name: Shalaka Joshi, MS, MCh
phone: 9869089803
phone ext: 4265
email: drjoshishalaka@gmail.com
last name: Rohini A Hawaldar
phone: 09820432613
email: rwhawaldar@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: India
citation: Semenza GL. Cancer-stromal cell interactions mediated by hypoxia-inducible factors promote angiogenesis, lymphangiogenesis, and metastasis. Oncogene. 2013 Aug 29;32(35):4057-63. doi: 10.1038/onc.2012.578. Epub 2012 Dec 10.
PMID: 23222717
citation: Hockel M, Vaupel P. Biological consequences of tumor hypoxia. Semin Oncol. 2001 Apr;28(2 Suppl 8):36-41.
PMID: 11395851
citation: Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer. 2013 Aug 2;12:86. doi: 10.1186/1476-4598-12-86.
PMID: 23915189
responsible party type: Principal Investigator
investigator affiliation: Tata Memorial Centre
investigator full name: Dr Rajendra A. Badwe
investigator title: Director, Tata Memorial Centre and Professor, Department of Surgical Oncology
mesh term: Breast Neoplasms
mesh term: Hypoxia
sharing ipd: Undecided