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/NCT06039956</url>
    </required_header>
    <id_info>
      <org_study_id>0004553</org_study_id>
      <nct_id>NCT06039956</nct_id>
    </id_info>
    <brief_title>De-escalating Axillary Surgery in Breast Cancer Patients in Nigeria</brief_title>
    <official_title>De-escalating Axillary Surgery After Neoadjuvant Chemotherapy in Node Positive Breast Cancer Patients in Nigeria</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Nova Scotia Health Authority</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Obafemi Awolowo University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Nova Scotia Health Authority</source>
    <oversight_info>
      <has_dmc>No</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>
        In sub-Saharan Africa, breast cancer patients often present with advanced disease. In my&#xD;
        previous research which evaluated over 600 patients from a prospective institutional data&#xD;
        base, about 64% of women with a new diagnosis of breast cancer presented with locally&#xD;
        advanced disease, including clinically positive axillary adenopathy. Our data also suggests&#xD;
        that similar to African American women, triple negative breast cancer (TNBC) is common in&#xD;
        Nigeria (43.5%).&#xD;
  &#xD;
        The overall goal of the project is to evaluate the ability of existing technology in Nigeria&#xD;
        to safely de-escalate axillary surgery in the management of locally advanced breast cancer&#xD;
        patients. Currently, the standard-of-care for breast cancer patients with palpable axillary&#xD;
        adenopathy (clinical N1 disease without evidence of distant metastases) at presentation in&#xD;
        Nigeria is neoadjuvant systemic therapy followed by a modified radical mastectomy. This&#xD;
        includes a complete axillary lymph node dissection (ALND). However, data from high-income&#xD;
        countries however show that up to 85% of patients initially presenting with cN1 disease can&#xD;
        be converted to cN0 (i.e. no palpable adenopathy) following NAC. These patients can thus&#xD;
        safely undergo sentinel lymph node biopsy (SLNB) with up to 50% of these having pathologic&#xD;
        complete response in the lymph nodes. In this patient population, both methylene blue and&#xD;
        radio-isotope localization with Tc-99 sulphur colloid are required to ensure adequate&#xD;
        performance of the SLNB to stage the axilla(i.e. false negative rate ≤10%). Although widely&#xD;
        available in high-income countries, radio-isotope localization is not readily available in&#xD;
        Nigeria. This project will explore an alternative to dual agent SLNB localization using&#xD;
        readily available resources and multi-disciplinary collaboration in a lower-income&#xD;
        environment. De-escalation of axillary surgery in high-income countries has significantly&#xD;
        decreased operative morbidity and improved patient reported outcomes without compromising&#xD;
        survival. However, context specific research and data from resource limited environments is&#xD;
        needed to translate the benefit of de-escalation to sub-Saharan Africa.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The overall goal of my research is to promote the delivery of guideline-concordant breast&#xD;
        cancer care to Nigerian breast cancer patients in a pragmatic manner. This project is novel&#xD;
        in that the investigators are challenging the existing paradigm of dual agent localization,&#xD;
        which is appropriate for a high-income setting, but completely out of reach and thus&#xD;
        inapplicable in Nigeria despite the obvious need. I will leverage the African Research Group&#xD;
        for Oncology (ARGO) breast cancer data base at OAUTHC and other existing research&#xD;
        infrastructure to pursue the following specific aims: Aim 1: Determine the false negative&#xD;
        rate of of axillary Ultrasound + single agent sentinel Lymph node biopsy in staging the&#xD;
        axilla in cN1 patients who become cN0. The investigators will consent patients with complete&#xD;
        clinical complete response (clinical assessment and targeted US) following NAC, for SLNB&#xD;
        followed by immediate ALND. Presence or absence of residual disease will be reported&#xD;
        separately for the SLNB and the ALND specimens. Positive axillary disease will be defined in&#xD;
        a binary manner as any invasive disease (including isolated tumor cells) or not. Using ALND&#xD;
        reporting as the gold standard, the investigators hypothesize a FNR of less than 10%&#xD;
        following SLNB. Aim 2: To determine the proportion of patients with complete axillary LN&#xD;
        Clinical &amp;Pathological cR post NAC. The proportion of patients who return negative for cancer&#xD;
        cells following SLNB and or ALND will be determined based on the number of patients with&#xD;
        preoperative node positive disease. Both overall pCR and subgroup analysis based on receptor&#xD;
        status will be done. The investigators will also assess the concordance of pre-operative&#xD;
        clinical and radiographic (i.e. targeted axillary US) assessment of lymph node status with&#xD;
        and pathologic lymph node status after NAC. The investigators hypothesize a pCR rate of 50%&#xD;
        following completion of NAC&#xD;
  &#xD;
        This study will build on the peer-reviewed analysis of our own prospective data demonstrating&#xD;
        a high incidence of locally advanced disease and chemo-sensitive subtypes (i.e. TNBC), which&#xD;
        suggest that a large proportion of our patients may be candidates for de-escalation. The&#xD;
        impact of de-escalation would be profound. Preliminary research into lymphedema as a result&#xD;
        of ALND in our patient population suggest an incidence of &gt; 35%. The proposed study will&#xD;
        provide a strong foundation for future studies evaluating the implementation of this strategy&#xD;
        and other resource compatible interventions on breast cancer outcomes in Nigeria.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">May 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">May 31, 2025</primary_completion_date>
    <phase>N/A</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>False-negative rate</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• False negative rate (FNR) of pre-op axillary US and single agent SLNB post-NAC for axillary staging</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>pathologic complete response rate</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• Incidence of axillary lymph node clinical and pathologic complete response in patient receiving NAC in Nigeria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>radiographic and clinical concordance</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• Concordance of pre-operative clinical, radiographic and pathologic lymph node status after NAC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sensitivity of pre-operative axillary US</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• Performance of pre-operative axillary US to stage the axilla in node positive patients who are cN0 disease after NAC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Specificity of pre-operative axillary US</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• Performance of pre-operative axillary US to stage the axilla in node positive patients who are cN0 disease after NAC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>False negative rate of pre-operative axillary US</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• Performance of pre-operative axillary US to stage the axilla in node positive patients who are cN0 disease after NAC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sensitivity of single-agent sentinel lymph node biopsy</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• Performance of single agent SLNB using methylene blue to stage the axilla in node positive patients who are cN0 disease after NAC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Specificity of single-agent sentinel lymph node biopsy</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• Performance of single agent SLNB using methylene blue to stage the axilla in node positive patients who are cN0 disease after NAC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>False negative rate of single-agent sentinel lymph node biopsy</measure>
      <time_frame>immediately after surgery</time_frame>
      <description>• Performance of single agent SLNB using methylene blue to stage the axilla in node positive patients who are cN0 disease after NAC</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Breast Cancer</condition>
    <condition>Axilla; Breast</condition>
    <arm_group>
      <arm_group_label>Sentinel Lymph Node Biopsy Arm</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Patients with non-metastatic, biopsy and clipped locally advanced breast cancer will start systemic chemotherapy as per institutional best practices. Patients with a clinical complete response will be consented for SLNB followed by immediate ALND. Patients with persistent suspicious clinical adenopathy will be consented for ALND alone. All patients regardless of response to NAC will undergo ALND as per current institutional practices.&#xD;
  Patients undergoing SLNB followed by ALND will have the procedure performed by study the co-PI at OAUTH who is trained in the performance of SLNB. Histopathologic assessment of the breast and axillary contents will follow a standardized reporting procedure, including the assessment of residual cancer burden in both the breast and the axilla. Presence or absence of residual disease will be reported separately for the SLNB specimens, clipped node and remaining axillary contents.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Sentinel lymph Node Biopsy</intervention_name>
      <description>The SLNB will be performed with 5 ml of undiluted methylene blue injected in equal aliquots, peri-tumoral, followed by a 5-minute massage prior to skin incision. Sentinel nodes will be defined as those that have uptake / visible blue staining or suspicious palpable nodes at the discretion of the operating surgeon. Sentinel nodes will be placed in formalin and sent separately. This will be followed by an immediate completion ALND, which will be similarly placed in formalin and sent separately from the SLNB specimen. Specimen radiographs will be performed on all specimens to confirm location of clip within SLNB vs. ALND specimens.</description>
      <arm_group_label>Sentinel Lymph Node Biopsy Arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Eligible to receive systemic chemotherapy&#xD;
  &#xD;
          Must include all the following:&#xD;
  &#xD;
            -  Tany, cN1 at presentation&#xD;
  &#xD;
            -  Biopsy proven pN1 disease after axillary US&#xD;
  &#xD;
            -  cN0 after neoadjuvant chemotherapy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Previous / recurrent breast cancer&#xD;
  &#xD;
            -  Previous axillary and/or breast surgery&#xD;
  &#xD;
            -  Inflammatory breast cancer&#xD;
  &#xD;
            -  N2 disease or Stage IV disease&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Olalekan Olasenhinde, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Obafemi Awolowo University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Gregory Knapp, MD</last_name>
      <phone>902-472-1523</phone>
      <email>gregory.knapp@nshealth.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Olalekan Olasehinde, MD</last_name>
      <email>lekanolasehinde@yahoo.com</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>April 11, 2023</study_first_submitted>
    <study_first_submitted_qc>September 13, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>neoadjuvant</keyword>
    <keyword>de-escalation</keyword>
    <keyword>breast cancer</keyword>
    <keyword>axillary lymph node staging</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
    </condition_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/NCT06039956
  org study id: 0004553
  nct id: NCT06039956
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  In sub-Saharan Africa, breast cancer patients often present with advanced disease. In my
        previous research which evaluated over 600 patients from a prospective institutional data
        base, about 64% of women with a new diagnosis of breast cancer presented with locally
        advanced disease, including clinically positive axillary adenopathy. Our data also suggests
        that similar to African American women, triple negative breast cancer (TNBC) is common in
        Nigeria (43.5%).
  
        The overall goal of the project is to evaluate the ability of existing technology in Nigeria
        to safely de-escalate axillary surgery in the management of locally advanced breast cancer
        patients. Currently, the standard-of-care for breast cancer patients with palpable axillary
        adenopathy (clinical N1 disease without evidence of distant metastases) at presentation in
        Nigeria is neoadjuvant systemic therapy followed by a modified radical mastectomy. This
        includes a complete axillary lymph node dissection (ALND). However, data from high-income
        countries however show that up to 85% of patients initially presenting with cN1 disease can
        be converted to cN0 (i.e. no palpable adenopathy) following NAC. These patients can thus
        safely undergo sentinel lymph node biopsy (SLNB) with up to 50% of these having pathologic
        complete response in the lymph nodes. In this patient population, both methylene blue and
        radio-isotope localization with Tc-99 sulphur colloid are required to ensure adequate
        performance of the SLNB to stage the axilla(i.e. false negative rate ≤10%). Although widely
        available in high-income countries, radio-isotope localization is not readily available in
        Nigeria. This project will explore an alternative to dual agent SLNB localization using
        readily available resources and multi-disciplinary collaboration in a lower-income
        environment. De-escalation of axillary surgery in high-income countries has significantly
        decreased operative morbidity and improved patient reported outcomes without compromising
        survival. However, context specific research and data from resource limited environments is
        needed to translate the benefit of de-escalation to sub-Saharan Africa.
  The overall goal of my research is to promote the delivery of guideline-concordant breast
        cancer care to Nigerian breast cancer patients in a pragmatic manner. This project is novel
        in that the investigators are challenging the existing paradigm of dual agent localization,
        which is appropriate for a high-income setting, but completely out of reach and thus
        inapplicable in Nigeria despite the obvious need. I will leverage the African Research Group
        for Oncology (ARGO) breast cancer data base at OAUTHC and other existing research
        infrastructure to pursue the following specific aims: Aim 1: Determine the false negative
        rate of of axillary Ultrasound + single agent sentinel Lymph node biopsy in staging the
        axilla in cN1 patients who become cN0. The investigators will consent patients with complete
        clinical complete response (clinical assessment and targeted US) following NAC, for SLNB
        followed by immediate ALND. Presence or absence of residual disease will be reported
        separately for the SLNB and the ALND specimens. Positive axillary disease will be defined in
        a binary manner as any invasive disease (including isolated tumor cells) or not. Using ALND
        reporting as the gold standard, the investigators hypothesize a FNR of less than 10%
        following SLNB. Aim 2: To determine the proportion of patients with complete axillary LN
        Clinical &Pathological cR post NAC. The proportion of patients who return negative for cancer
        cells following SLNB and or ALND will be determined based on the number of patients with
        preoperative node positive disease. Both overall pCR and subgroup analysis based on receptor
        status will be done. The investigators will also assess the concordance of pre-operative
        clinical and radiographic (i.e. targeted axillary US) assessment of lymph node status with
        and pathologic lymph node status after NAC. The investigators hypothesize a pCR rate of 50%
        following completion of NAC
  
        This study will build on the peer-reviewed analysis of our own prospective data demonstrating
        a high incidence of locally advanced disease and chemo-sensitive subtypes (i.e. TNBC), which
        suggest that a large proportion of our patients may be candidates for de-escalation. The
        impact of de-escalation would be profound. Preliminary research into lymphedema as a result
        of ALND in our patient population suggest an incidence of > 35%. The proposed study will
        provide a strong foundation for future studies evaluating the implementation of this strategy
        and other resource compatible interventions on breast cancer outcomes in Nigeria.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: False-negative rate
  time frame: immediately after surgery
  description: • False negative rate (FNR) of pre-op axillary US and single agent SLNB post-NAC for axillary staging
  measure: pathologic complete response rate
  time frame: immediately after surgery
  description: • Incidence of axillary lymph node clinical and pathologic complete response in patient receiving NAC in Nigeria
  measure: radiographic and clinical concordance
  time frame: immediately after surgery
  description: • Concordance of pre-operative clinical, radiographic and pathologic lymph node status after NAC
  measure: Sensitivity of pre-operative axillary US
  time frame: immediately after surgery
  description: • Performance of pre-operative axillary US to stage the axilla in node positive patients who are cN0 disease after NAC
  measure: Specificity of pre-operative axillary US
  time frame: immediately after surgery
  description: • Performance of pre-operative axillary US to stage the axilla in node positive patients who are cN0 disease after NAC
  measure: False negative rate of pre-operative axillary US
  time frame: immediately after surgery
  description: • Performance of pre-operative axillary US to stage the axilla in node positive patients who are cN0 disease after NAC
  measure: Sensitivity of single-agent sentinel lymph node biopsy
  time frame: immediately after surgery
  description: • Performance of single agent SLNB using methylene blue to stage the axilla in node positive patients who are cN0 disease after NAC
  measure: Specificity of single-agent sentinel lymph node biopsy
  time frame: immediately after surgery
  description: • Performance of single agent SLNB using methylene blue to stage the axilla in node positive patients who are cN0 disease after NAC
  measure: False negative rate of single-agent sentinel lymph node biopsy
  time frame: immediately after surgery
  description: • Performance of single agent SLNB using methylene blue to stage the axilla in node positive patients who are cN0 disease after NAC
  arm group label: Sentinel Lymph Node Biopsy Arm
  arm group type: Other
  description: Patients with non-metastatic, biopsy and clipped locally advanced breast cancer will start systemic chemotherapy as per institutional best practices. Patients with a clinical complete response will be consented for SLNB followed by immediate ALND. Patients with persistent suspicious clinical adenopathy will be consented for ALND alone. All patients regardless of response to NAC will undergo ALND as per current institutional practices.
  Patients undergoing SLNB followed by ALND will have the procedure performed by study the co-PI at OAUTH who is trained in the performance of SLNB. Histopathologic assessment of the breast and axillary contents will follow a standardized reporting procedure, including the assessment of residual cancer burden in both the breast and the axilla. Presence or absence of residual disease will be reported separately for the SLNB specimens, clipped node and remaining axillary contents.
  intervention type: Procedure
  intervention name: Sentinel lymph Node Biopsy
  description: The SLNB will be performed with 5 ml of undiluted methylene blue injected in equal aliquots, peri-tumoral, followed by a 5-minute massage prior to skin incision. Sentinel nodes will be defined as those that have uptake / visible blue staining or suspicious palpable nodes at the discretion of the operating surgeon. Sentinel nodes will be placed in formalin and sent separately. This will be followed by an immediate completion ALND, which will be similarly placed in formalin and sent separately from the SLNB specimen. Specimen radiographs will be performed on all specimens to confirm location of clip within SLNB vs. ALND specimens.
  arm group label: Sentinel Lymph Node Biopsy Arm
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Olalekan Olasenhinde, MD
  role: Principal Investigator
  affiliation: Obafemi Awolowo University
  last name: Gregory Knapp, MD
  phone: 902-472-1523
  email: gregory.knapp@nshealth.ca
  last name: Olalekan Olasehinde, MD
  email: lekanolasehinde@yahoo.com
  responsible party type: Sponsor
  mesh term: Breast Neoplasms