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/NCT05982678</url>
    </required_header>
    <id_info>
      <org_study_id>M22BOL</org_study_id>
      <nct_id>NCT05982678</nct_id>
    </id_info>
    <brief_title>Basket Study for Oligo-metastatic Breast Cancer</brief_title>
    <acronym>ANISE</acronym>
    <official_title>Basket Study for Oligo-metastatic Breast Cancer Part 1: Trastuzumab-deruxtecan for HER2-positive Oligo-metastatic Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>The Netherlands Cancer Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Daiichi Sankyo, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>AstraZeneca</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>The Netherlands Cancer Institute</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>
        The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic&#xD;
        lesions, all amenable for curative intervention. Patients will be stratified by prior therapy&#xD;
        and ER expression. In the initial baskets patients with be treated with&#xD;
        trastuzumab-deruxtecan.&#xD;
  &#xD;
        Patients are treated with T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of&#xD;
        16 cycles leading to a treatment period of year, including local treatment. The first 8&#xD;
        cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of&#xD;
        local treatment.&#xD;
  &#xD;
        The proposed M22BOL trial is based on an important knowledge gap for regarding breast cancer&#xD;
        patients with 'oligo-metastatic' disease who are usually not included in clinical trials for&#xD;
        patients with metastatic disease since loco-regional treatments (radiation, surgery) with&#xD;
        curative intent is not allowed in clinical trials for metastatic breast cancer. Moreover,&#xD;
        neo-adjuvant trial protocols for early breast cancer exclude patients with distant metastases&#xD;
        that can be treated with curative intent. This basket trial evaluates T-DXd for&#xD;
        oligo-metastatic breast cancer with the goal to induce deep responses and subsequently&#xD;
        long-lasting disease remissions and potentially cure.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic&#xD;
        lesions, all amenable for curative intervention. Patients will be stratified by prior therapy&#xD;
        and ER expression. Given the basket-design of this trial other baskets for oligo-metastatic&#xD;
        breast cancer can be added, such as but not limited to other breast cancer subtypes or with&#xD;
        other promising drugs.&#xD;
  &#xD;
        Baskets for de novo oligo-metastatic disease I. ER+/HER2+ II. ER-/HER2+ Baskets for&#xD;
        oligo-metastatic disease after prior chemo/anti-HER2 therapy for primary disease III.&#xD;
        ER+/HER2+ IV. ER-/HER2+&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2034</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2027</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>Complete radiologic response</measure>
      <time_frame>up to one year after start treatment</time_frame>
      <description>Number of patients to achieve radiologic response as defined by RECIST 11 with clearnace of ctDNA</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of patients free of progression</measure>
      <time_frame>assessed up to 10 years</time_frame>
      <description>as defined by RECIST</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival</measure>
      <time_frame>assessed up to 10 years</time_frame>
      <description>time from start treatment to death from any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of patients with pathological complete response</measure>
      <time_frame>assessed immediately after surgery</time_frame>
      <description>after resection of primary tumor and/or metastatic lesions after neo-adjuvant treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of patients with metabolic response</measure>
      <time_frame>assessed up to 12 months</time_frame>
      <description>as measured with PDG-PET</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of patients with metabolic response</measure>
      <time_frame>assessed up to 10 years</time_frame>
      <description>as measured by clearance of ctDNA</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)</measure>
      <time_frame>assessed up to 30 days after last treatment</time_frame>
      <description>determined accoriding to CTCAE v5.0 or Clavien-Dindo (in case of surgical resection)</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">72</enrollment>
    <condition>HER2-positive Breast Cancer</condition>
    <arm_group>
      <arm_group_label>Trastuzumab-deruxtecan</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Trastuzumab deruxtecan</intervention_name>
      <description>T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.</description>
      <arm_group_label>Trastuzumab-deruxtecan</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Histologic proof of infiltrating HER2-positive breast cancer (as determined by IHC 3+&#xD;
               and/or amplification by ISH)[8]&#xD;
  &#xD;
            -  Histologic or cytologic proof of breast cancer metastases (at least one lesion)&#xD;
  &#xD;
            -  Histologic determination of level of ER-expression&#xD;
  &#xD;
            -  Oligo-metastatic disease as determined by standard of care diagnostics. The number of&#xD;
               total individual distant metastases is limited to three, either in one organ or in 2-3&#xD;
               organ systems. Clustered lymph nodes that can be irradiated with curative intent in a&#xD;
               single field are defined as single lesion. Pleuritis carcinomatosa, miliary spread of&#xD;
               metastases (even within one organ), or peritoneal spread of metastases rules out&#xD;
               oligo-metastatic disease and is not allowed. Initial staging by PET-CT (whole body)&#xD;
               and MRI of breast and brain are mandatory, as is MRI liver or spine and pelvis in case&#xD;
               of liver or bone metastases respectively.&#xD;
  &#xD;
            -  In case of recurrent disease, a disease-free interval of 24 months.&#xD;
  &#xD;
            -  Measurable disease according to RECIST1.1&#xD;
  &#xD;
            -  Patients must be at least 18 years of age and be able to give written informed consent&#xD;
               and comply with study procedures.&#xD;
  &#xD;
            -  World Health Organization (WHO) performance status 0 or 1&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  prior line of therapy for metastatic disease. Exceptions are endocrine therapy or&#xD;
               radiation considered to be part of the curative treatment, within 3 months before&#xD;
               enrolment&#xD;
  &#xD;
            -  leptomeningeal disease or central nervous metastases&#xD;
  &#xD;
            -  clinically relevant obstruction or compression of spinal cord, central nervous,&#xD;
               gastro-intestinal or cardiovascular system, that cannot be alleviated before start of&#xD;
               treatment.&#xD;
  &#xD;
            -  other malignancy, unless treated with curative intention and a long-term survival&#xD;
               probability of &gt;95%, including in-situ or pre-malignant lesions.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Marleen Kok, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Antoni van Leeuwenhoek</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Marleen Kok, MD</last_name>
      <phone>+31205129111</phone>
      <phone_ext>9111</phone_ext>
      <email>m.kok@nki.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Robbert-Jan Gielen, MD</last_name>
      <phone>+3120512</phone>
      <phone_ext>9111</phone_ext>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Antoni van Leeuwenhoek</name>
        <address>
          <city>Amsterdam</city>
          <country>Netherlands</country>
        </address>
      </facility>
      <contact>
        <last_name>Robbert-Jan Gielen, MD</last_name>
      </contact>
      <contact_backup>
        <last_name>Ingrid Mandjes, MSc</last_name>
      </contact_backup>
      <investigator>
        <last_name>Marleen Kok, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Oligometastatic disease (max 3 lesions)</keyword>
    <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>Trastuzumab</mesh_term>
      <mesh_term>Trastuzumab deruxtecan</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>to de decided</ipd_description>
    </patient_data>
    <!-- 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/NCT05982678
  org study id: M22BOL
  nct id: NCT05982678
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic
        lesions, all amenable for curative intervention. Patients will be stratified by prior therapy
        and ER expression. In the initial baskets patients with be treated with
        trastuzumab-deruxtecan.
  
        Patients are treated with T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of
        16 cycles leading to a treatment period of year, including local treatment. The first 8
        cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of
        local treatment.
  
        The proposed M22BOL trial is based on an important knowledge gap for regarding breast cancer
        patients with 'oligo-metastatic' disease who are usually not included in clinical trials for
        patients with metastatic disease since loco-regional treatments (radiation, surgery) with
        curative intent is not allowed in clinical trials for metastatic breast cancer. Moreover,
        neo-adjuvant trial protocols for early breast cancer exclude patients with distant metastases
        that can be treated with curative intent. This basket trial evaluates T-DXd for
        oligo-metastatic breast cancer with the goal to induce deep responses and subsequently
        long-lasting disease remissions and potentially cure.
  The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic
        lesions, all amenable for curative intervention. Patients will be stratified by prior therapy
        and ER expression. Given the basket-design of this trial other baskets for oligo-metastatic
        breast cancer can be added, such as but not limited to other breast cancer subtypes or with
        other promising drugs.
  
        Baskets for de novo oligo-metastatic disease I. ER+/HER2+ II. ER-/HER2+ Baskets for
        oligo-metastatic disease after prior chemo/anti-HER2 therapy for primary disease III.
        ER+/HER2+ IV. ER-/HER2+
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Complete radiologic response
  time frame: up to one year after start treatment
  description: Number of patients to achieve radiologic response as defined by RECIST 11 with clearnace of ctDNA
  measure: Number of patients free of progression
  time frame: assessed up to 10 years
  description: as defined by RECIST
  measure: Overall Survival
  time frame: assessed up to 10 years
  description: time from start treatment to death from any cause
  measure: Number of patients with pathological complete response
  time frame: assessed immediately after surgery
  description: after resection of primary tumor and/or metastatic lesions after neo-adjuvant treatment
  measure: Number of patients with metabolic response
  time frame: assessed up to 12 months
  description: as measured with PDG-PET
  measure: Number of patients with metabolic response
  time frame: assessed up to 10 years
  description: as measured by clearance of ctDNA
  measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
  time frame: assessed up to 30 days after last treatment
  description: determined accoriding to CTCAE v5.0 or Clavien-Dindo (in case of surgical resection)
  arm group label: Trastuzumab-deruxtecan
  arm group type: Experimental
  description: 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.
  intervention type: Drug
  intervention name: Trastuzumab deruxtecan
  description: T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.
  arm group label: Trastuzumab-deruxtecan
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Marleen Kok, MD
  role: Principal Investigator
  affiliation: Antoni van Leeuwenhoek
  last name: Marleen Kok, MD
  phone: +31205129111
  phone ext: 9111
  email: m.kok@nki.nl
  last name: Robbert-Jan Gielen, MD
  phone: +3120512
  phone ext: 9111
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: Netherlands
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  mesh term: Trastuzumab
  mesh term: Trastuzumab deruxtecan
  sharing ipd: Undecided
  ipd description: to de decided