<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/NCT04399876</url>
  </required_header>
  <id_info>
    <org_study_id>19-599</org_study_id>
    <secondary_id>R01CA232174</secondary_id>
    <nct_id>NCT04399876</nct_id>
  </id_info>
  <brief_title>Pilot Study of an Implantable Microdevice for Evaluating Drug Responses in Situ in Prostate Cancer</brief_title>
  <official_title>Pilot Study of an Implantable Microdevice for Evaluating Drug Responses in Situ in Prostate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this research study, is assessing the feasibility of using an MR-guided implantable&#xD;
      microdevice to measure tumor response to chemotherapy and other clinically relevant drugs in&#xD;
      participants that have prostate cancer and are scheduled for a radical prostatectomy.&#xD;
&#xD;
      The name of the study intervention involved in this study is:&#xD;
&#xD;
      - Implantation of a MR-guided microdevice&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is assessing the feasibility and safety of implanting and retrieving a&#xD;
      'microdevice' that releases up to 20 drugs directly within the prostate cancer lesion as a&#xD;
      possible tool to evaluate the effectiveness of several approved cancer drugs against prostate&#xD;
      cancer.&#xD;
&#xD;
      Participants will be identified with confirmed prostate cancer whose treatment plan includes&#xD;
      surgery as a component of standard-of-care treatment.&#xD;
&#xD;
      The name of the study intervention involved in this study is:&#xD;
&#xD;
        -  Implantation of a MR-guided microdevice .&#xD;
&#xD;
        -  It is expected that about 35 people will take part in this research study; 5 in the Ex&#xD;
           Vivo Cohort and 30 in Surgery Cohort.&#xD;
&#xD;
             -  Ex Vivo Cohort will undergo placement of microdevice in the prostate after its&#xD;
                surgical removal.&#xD;
&#xD;
             -  Surgery Cohort will undergo percutaneous placement of several microdevices in a&#xD;
                selected tumor prior to surgery.&#xD;
&#xD;
      This research study is a Pilot Study, which is the first-time investigators are examining&#xD;
      this study intervention. The FDA (the U.S. Food and Drug Administration) has not approved the&#xD;
      implantation of the microdevice for this specific disease, but usage of this has been&#xD;
      approved for other uses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">June 22, 2020</start_date>
  <completion_date type="Anticipated">March 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2025</primary_completion_date>
  <phase>Phase 1</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events as defined in the CTCAE v4.0</measure>
    <time_frame>From the time of arrival to interventional radiology for microdevice placement up to 6 weeks.</time_frame>
    <description>Safety of microdevice placement and removal based on assessment of adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with successful surgical Placement and retrieval of Microdevice</measure>
    <time_frame>48 Hours</time_frame>
    <description>Feasibility of microdevice placement based on the ability in the Surgical Cohort to percutaneously place and surgically retrieve the device with sufficient tissue, of sufficient quality, for downstream histopathology analysis and interpretation.&#xD;
In the Surgical Cohort, if not more than 1 IMD per patient fails to be percutaneously placed and surgically retrieved with sufficient tissue of sufficient quality for downstream histopathology analysis and interpretation, we would consider this procedure to be a success. If at least 23/30 Surgical Cohort patients have successful procedures, as previously defined, we would consider this approach feasible. The 90% CI for 23 out of 30 successes is (60.6%, 88.5%) and thus excluding a 60% success rate which is considered as too low.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local intratumor response</measure>
    <time_frame>48 Hours</time_frame>
    <description>measure local intratumor response to clinically relevant cytotoxic agents and small molecule drugs in prostate cancers using quantitative histopathologic assessment of tumor tissue.&#xD;
All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates. Descriptive statistics will be used to summarize the quantitative measurements of apoptosis, proliferation, DNA repair, etc. for drug-treated regions compared to vehicle-treated regions. At least two separate regions will contain vehicle to account for tumor heterogeneity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intratumor heterogeneity in drug response</measure>
    <time_frame>48 Hours</time_frame>
    <description>comparing the extent of tumor response to drug among different locations in a single tumor with multiple microdevice.&#xD;
All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers of drug response</measure>
    <time_frame>48 Hours</time_frame>
    <description>immune infiltrates, in the local tumor tissue adjacent to the microdevice, and to perform a preliminary assessment of the correlation between these features and extent of tumor response with the microdevice All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic features of the tumor tissue</measure>
    <time_frame>48 Hours</time_frame>
    <description>To determine the genetic features of the tumor tissue adjacent to the microdevice (e.g. whole exome sequencing, whole transcriptome sequencing) and to perform a preliminary assessment of the correlation between known genetic markers of drug sensitivity or resistance and extent of tumor response with the microdevice Genetic alterations will be catalogued in terms of single nucleotide variants, insertions/deletions, and copy number changes and will be primarily reported in a descriptive manner. Preliminary correlations between a specific genetic feature and specific clinical features will be tested using the Chi-squared/Fisher's exact test for categorical variables or the T-test or Wilcoxon Rank-Sum test for continuous variables</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Prostate Cancer</condition>
  <condition>Radical Prostatectomy</condition>
  <arm_group>
    <arm_group_label>Surgery Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant eligibility for intervention and selection of lesion for device placement&#xD;
- Surgery Cohort will undergo percutaneous placement of several microdevices in a selected tumor(s) prior to surgery. The microdevice in the surgery cohort will dwell in the tumor tissue for approximately 48 hours to allow time for tissue effects of the drugs in the microdevice reservoirs.&#xD;
Placement of at least 1, and up to 6, microdevices depending on the number of lesions, size and accessibility&#xD;
Extirpative surgery will proceed according to standard-of-care procedures. The microdevice(s) will be removed surgically along with surrounding tumor tissue.&#xD;
Standard of care treatment and follow-up of clinical course</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ex-Vivo Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will undergo a screening process to determine their eligibility for microdevice placement, consisting of the following items:&#xD;
Routine standard of care for radical prostatectomy.&#xD;
Placement of implantable microdevice with multiple miniature drug reservoirs but no drug in prostate that have been removed&#xD;
Ex vivo image guided removal using retrieval device&#xD;
Standard of Care Treatment and follow-up of clinical course</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Microdevice</intervention_name>
    <description>Surgery Cohort: Placement of 1-6 microdevices: Drugs chosen have all been FDA approved for the treatment of cancer (so therefore safe) and there are phase 2 or 3 data that the drug has efficacy in prostate cancer. Agents of interest included Abiraterone, Enzalutamide, Pembrolizumab, Ipilimumab, Carboplatin, Docetaxel, and Olaparib as well as combinations&#xD;
Ex vivo Cohort: Placement of multiple microdevices with miniature drug reservoirs but no drug is loaded into the removed prostate</description>
    <arm_group_label>Ex-Vivo Cohort</arm_group_label>
    <arm_group_label>Surgery Cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eligibility Criteria Ex Vivo Cohort&#xD;
&#xD;
               -  Participants must have the ability to understand and the willingness to sign a&#xD;
                  written informed consent document.&#xD;
&#xD;
               -  Planned Radical Prostatectomy for Prostate Cancer.&#xD;
&#xD;
               -  Participants must be 22 years of age or older.&#xD;
&#xD;
          -  Eligibility Criteria for Surgical Cohort&#xD;
&#xD;
               -  Participants must have the ability to understand and the willingness to sign a&#xD;
                  written informed consent document.&#xD;
&#xD;
               -  Participants must present with prostate cancer falling into an intermediate or&#xD;
                  high risk category to include features: Gleason score 3+4 or higher, greater than&#xD;
                  3 biopsy cores positive and &gt;50% of 1 core positive for carcinoma, and an&#xD;
                  MRI-visible lesion concerning for PCa in the region of the positive biopsy.&#xD;
&#xD;
               -  Participants must be 22 years of age or older.&#xD;
&#xD;
               -  Participants must be evaluated by a urologic oncologist who will determine the&#xD;
                  clinically appropriate treatment strategy based on clinical history and extent of&#xD;
                  disease.&#xD;
&#xD;
               -  Participants must be deemed medically stable to undergo both percutaneous&#xD;
                  procedures and standard-of-care surgical procedures by their treating surgeon.&#xD;
&#xD;
               -  Participants will undergo laboratory testing within 30 days prior to the&#xD;
                  procedure (or within 72 hours if there has been a change in the clinical status&#xD;
                  since the initial blood draw). Participants must have absolute neutrophil count&#xD;
                  ≥1,500/mcL, platelets ≥50,000/mcL, PT (INR) 0.8-1.2 and PTT within the normal&#xD;
                  range of the institution.&#xD;
&#xD;
               -  Participants must have undergone multi-parametric prostate MRI that both assesses&#xD;
                  the extent of disease and allows the research team to assess for study&#xD;
                  eligibility. This will have been done as part of the standard-of-care. Abnormal&#xD;
                  imaging will be correlated with the biopsy findings to maximize the likelihood of&#xD;
                  the device being put in the lesion. If the images are not adequate, the MRI scan&#xD;
                  will be repeated at BWH/DFCI, again as part of standard-of-care management.&#xD;
&#xD;
               -  The participant's case must be reviewed by representatives of urologic oncology&#xD;
                  and interventional radiology to assess the following factors:&#xD;
&#xD;
                    -  Participant is clinically stable to undergo biopsy procedure(s) and surgical&#xD;
                       procedures&#xD;
&#xD;
                    -  Participant has sufficient volume of disease as shown by MRI to allow&#xD;
                       implantation of the microdevice&#xD;
&#xD;
                    -  A lesion can be selected where the microdevice is to be implanted that is a)&#xD;
                       amenable to percutaneous placement, and b) amenable to removal at the time&#xD;
                       of primary surgery -- Participants must be willing to undergo&#xD;
                       research-related genetic sequencing (somatic and germline) and data&#xD;
                       management, including the deposition of de-identified genetic sequencing&#xD;
                       data in NIH central data repositories.&#xD;
&#xD;
          -  Exclusion Criteria:&#xD;
&#xD;
               -  Uncontrolled intercurrent illness including, but not limited to, ongoing or&#xD;
                  active infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
                  cardiac arrhythmia, or psychiatric illness/social situations that would limit the&#xD;
                  safety of a biopsy and/or surgery.&#xD;
&#xD;
               -  Uncorrectable bleeding or coagulation disorder known to cause increased risk with&#xD;
                  surgical or biopsy procedures (detailed below).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adam S Kibel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>August 16, 2022</last_update_submitted>
  <last_update_submitted_qc>August 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Adam Kibel, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Prostate Cancer</keyword>
  <keyword>Radical Prostatectomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
    <ipd_access_criteria>Contact the Partners Innovations team at http://www.partners.org/innovation</ipd_access_criteria>
  </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/NCT04399876
org study id: 19-599
secondary id: R01CA232174
nct id: NCT04399876
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In this research study, is assessing the feasibility of using an MR-guided implantable
      microdevice to measure tumor response to chemotherapy and other clinically relevant drugs in
      participants that have prostate cancer and are scheduled for a radical prostatectomy.

      The name of the study intervention involved in this study is:

      - Implantation of a MR-guided microdevice
This research study is assessing the feasibility and safety of implanting and retrieving a
      'microdevice' that releases up to 20 drugs directly within the prostate cancer lesion as a
      possible tool to evaluate the effectiveness of several approved cancer drugs against prostate
      cancer.

      Participants will be identified with confirmed prostate cancer whose treatment plan includes
      surgery as a component of standard-of-care treatment.

      The name of the study intervention involved in this study is:

        -  Implantation of a MR-guided microdevice .

        -  It is expected that about 35 people will take part in this research study; 5 in the Ex
           Vivo Cohort and 30 in Surgery Cohort.

             -  Ex Vivo Cohort will undergo placement of microdevice in the prostate after its
                surgical removal.

             -  Surgery Cohort will undergo percutaneous placement of several microdevices in a
                selected tumor prior to surgery.

      This research study is a Pilot Study, which is the first-time investigators are examining
      this study intervention. The FDA (the U.S. Food and Drug Administration) has not approved the
      implantation of the microdevice for this specific disease, but usage of this has been
      approved for other uses.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Number of participants with adverse events as defined in the CTCAE v4.0
time frame: From the time of arrival to interventional radiology for microdevice placement up to 6 weeks.
description: Safety of microdevice placement and removal based on assessment of adverse events
measure: Number of Participants with successful surgical Placement and retrieval of Microdevice
time frame: 48 Hours
description: Feasibility of microdevice placement based on the ability in the Surgical Cohort to percutaneously place and surgically retrieve the device with sufficient tissue, of sufficient quality, for downstream histopathology analysis and interpretation.
In the Surgical Cohort, if not more than 1 IMD per patient fails to be percutaneously placed and surgically retrieved with sufficient tissue of sufficient quality for downstream histopathology analysis and interpretation, we would consider this procedure to be a success. If at least 23/30 Surgical Cohort patients have successful procedures, as previously defined, we would consider this approach feasible. The 90% CI for 23 out of 30 successes is (60.6%, 88.5%) and thus excluding a 60% success rate which is considered as too low.
measure: Local intratumor response
time frame: 48 Hours
description: measure local intratumor response to clinically relevant cytotoxic agents and small molecule drugs in prostate cancers using quantitative histopathologic assessment of tumor tissue.
All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates. Descriptive statistics will be used to summarize the quantitative measurements of apoptosis, proliferation, DNA repair, etc. for drug-treated regions compared to vehicle-treated regions. At least two separate regions will contain vehicle to account for tumor heterogeneity.
measure: Intratumor heterogeneity in drug response
time frame: 48 Hours
description: comparing the extent of tumor response to drug among different locations in a single tumor with multiple microdevice.
All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates.
measure: Biomarkers of drug response
time frame: 48 Hours
description: immune infiltrates, in the local tumor tissue adjacent to the microdevice, and to perform a preliminary assessment of the correlation between these features and extent of tumor response with the microdevice All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates.
measure: Genetic features of the tumor tissue
time frame: 48 Hours
description: To determine the genetic features of the tumor tissue adjacent to the microdevice (e.g. whole exome sequencing, whole transcriptome sequencing) and to perform a preliminary assessment of the correlation between known genetic markers of drug sensitivity or resistance and extent of tumor response with the microdevice Genetic alterations will be catalogued in terms of single nucleotide variants, insertions/deletions, and copy number changes and will be primarily reported in a descriptive manner. Preliminary correlations between a specific genetic feature and specific clinical features will be tested using the Chi-squared/Fisher's exact test for categorical variables or the T-test or Wilcoxon Rank-Sum test for continuous variables
arm group label: Surgery Cohort
arm group type: Experimental
description: Participant eligibility for intervention and selection of lesion for device placement
- Surgery Cohort will undergo percutaneous placement of several microdevices in a selected tumor(s) prior to surgery. The microdevice in the surgery cohort will dwell in the tumor tissue for approximately 48 hours to allow time for tissue effects of the drugs in the microdevice reservoirs.
Placement of at least 1, and up to 6, microdevices depending on the number of lesions, size and accessibility
Extirpative surgery will proceed according to standard-of-care procedures. The microdevice(s) will be removed surgically along with surrounding tumor tissue.
Standard of care treatment and follow-up of clinical course
arm group label: Ex-Vivo Cohort
arm group type: Experimental
description: Each participant will undergo a screening process to determine their eligibility for microdevice placement, consisting of the following items:
Routine standard of care for radical prostatectomy.
Placement of implantable microdevice with multiple miniature drug reservoirs but no drug in prostate that have been removed
Ex vivo image guided removal using retrieval device
Standard of Care Treatment and follow-up of clinical course
intervention type: Combination Product
intervention name: Microdevice
description: Surgery Cohort: Placement of 1-6 microdevices: Drugs chosen have all been FDA approved for the treatment of cancer (so therefore safe) and there are phase 2 or 3 data that the drug has efficacy in prostate cancer. Agents of interest included Abiraterone, Enzalutamide, Pembrolizumab, Ipilimumab, Carboplatin, Docetaxel, and Olaparib as well as combinations
Ex vivo Cohort: Placement of multiple microdevices with miniature drug reservoirs but no drug is loaded into the removed prostate
arm group label: Ex-Vivo Cohort
arm group label: Surgery Cohort
criteria: 
gender: Male
minimum age: 22 Years
maximum age: N/A
healthy volunteers: No
last name: Adam S Kibel, MD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Adam Kibel, MD
investigator title: Principal Investigator
mesh term: Prostatic Neoplasms
sharing ipd: Yes
ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication
ipd access criteria: Contact the Partners Innovations team at http://www.partners.org/innovation