<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/NCT01676259</url>
  </required_header>
  <id_info>
    <org_study_id>SLSG12D-P2</org_study_id>
    <nct_id>NCT01676259</nct_id>
  </id_info>
  <brief_title>A Phase 2 Study of siG12D LODER in Combination With Chemotherapy in Patients With Locally Advanced Pancreatic Cancer</brief_title>
  <acronym>PROTACT</acronym>
  <official_title>A Prospective, Multinational, Multi-Center, Phase 2, Single-Arm, Open-Label Study Evaluating the Efficacy, Safety and Tolerability of siG12D-LODER in Combination With Standard of Care Chemotherapy in the Treatment of Patients With Locally Advanced Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Silenseed Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Silenseed Ltd</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 Phase II study a dose of 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered in&#xD;
      12-week cycles to patients with unresectable or borderline resectable locally advanced&#xD;
      pancreatic cancer combined with chemotherapy treatment.&#xD;
&#xD;
      Primary Outcome:&#xD;
&#xD;
      - ORR at 6 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this Phase II study a dose of 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered in&#xD;
      12-week cycles to patients with unresectable or borderline resectable LAPC combined with&#xD;
      chemotherapy treatment (Gemcitabine+nab-Paclitaxel or Folfirinox or modified Folfirinox).&#xD;
      This will be a study to assess the response rate of the siG12D-LODER in patients with&#xD;
      unresectable or borderline resectable LAPC. The study is of a single arm design with one arm&#xD;
      receiving siG12D-LODER + chemotherapy.&#xD;
&#xD;
      The investigational agent siG12D-LODER is a miniature biodegradable bio polymeric matrix that&#xD;
      encompasses the drug, designed and produced by Silenseed Ltd. The implantation of LODERs is&#xD;
      selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures,&#xD;
      proved to be highly effective and safe.&#xD;
&#xD;
      siG12D-LODER has been studied in the escalating dose Phase I study of 15 patients, and&#xD;
      results showed high safety and tolerability profiles, with no single DLT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 7, 2018</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2022</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>ORR at 6 months</measure>
    <time_frame>One year</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Pancreatic Ductal Adenocarcinoma</condition>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>siG12D-LODER + chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eight siG12D-LODER+Gemcitabine+nab-Paclitaxel or Eight siG12D-LODER+Folfirinox or Eight siG12D-LODER+modifide Folfirinox</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>siG12D-LODER</intervention_name>
    <description>The implantation of siG12D-LODERs is selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures, proved to be highly effective and safe.</description>
    <arm_group_label>siG12D-LODER + chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine+nab-Paclitaxel</intervention_name>
    <description>Gemcitabine+nab-Paclitaxel</description>
    <arm_group_label>siG12D-LODER + chemotherapy</arm_group_label>
    <other_name>Chemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Folfirinox</intervention_name>
    <description>Folfirinox or modified Folfirinox</description>
    <arm_group_label>siG12D-LODER + chemotherapy</arm_group_label>
    <other_name>Chemotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Age&#xD;
&#xD;
        1. Subject must be 18 years of age or older at the time of signing the informed consent.&#xD;
&#xD;
        Type of Subject and Disease Characteristics&#xD;
&#xD;
          1. Histologically or cytologically confirmed adenocarcinoma of the pancreas.&#xD;
&#xD;
          2. Locally advanced pancreatic cancer stage III according to The American Joint Committee&#xD;
             on Cancer (AJCC) and defined as T4, N (any) and M0, according to the three factors, T&#xD;
             (tumor), N (node involvement), and M (metastases), of the National Comprehensive&#xD;
             Cancer Network TNM classification.&#xD;
&#xD;
          3. Allocated to receive one of the following chemotherapies: gemcitabine plus&#xD;
             nab-paclitaxel, FOLFIRINOX or modified FOLFIRIONOX as first line treatment for&#xD;
             pancreatic cancer.&#xD;
&#xD;
          4. Have a target tumor that is accessible for intratumoral administration by EUS as&#xD;
             determined by the radiologist/gastroenterologist performing the EUS intratumoral&#xD;
             administration, according to The American Society for Gastrointestinal Endoscopy&#xD;
             (ASGE) guidelines (https://www.asge.org/home/practice-support/guidelines).&#xD;
&#xD;
          5. Have measurable disease. Subject will have a histologically-confirmed disease and must&#xD;
             have clinically and/or radiographically documented measurable primary disease&#xD;
             according to RECIST v1.1. At least one site of disease must be unidimensionally&#xD;
             measurable.&#xD;
&#xD;
             Diagnostic Assessments&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) Performance Scale of ≤ 1.&#xD;
&#xD;
          7. Demonstrate adequate organ function as defined below:&#xD;
&#xD;
               -  serum creatinine &lt;1.6 mg/dL&#xD;
&#xD;
               -  international normalized ratio (INR) &lt; 1.5 U&#xD;
&#xD;
               -  absolute neutrophil count (ANC) &gt; 1.5 x 109/L&#xD;
&#xD;
               -  platelets ≥ 100 x 109/L&#xD;
&#xD;
               -  hemoglobin ≥ 9 mg/dL&#xD;
&#xD;
               -  alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 5 times upper&#xD;
                  limit of normal (ULN)&#xD;
&#xD;
               -  bilirubin ≤ 1.5 x ULN Sex&#xD;
&#xD;
          8. Male and/or female. Contraceptive use by men or women should be consistent with local&#xD;
             regulations regarding the methods of contraception for those participating in clinical&#xD;
             studies.&#xD;
&#xD;
          9. Women of childbearing potential (WOCBP): a negative serum or urine pregnancy test&#xD;
             during screening.&#xD;
&#xD;
         10. Subject of childbearing potential, if sexually active (both men and women) must agree&#xD;
             to use a barrier method of contraception, from the time of administration of the first&#xD;
             treatment and for at least 8 weeks after EOT visit day.&#xD;
&#xD;
             Informed Consent&#xD;
&#xD;
         11. Capable of giving signed informed consent which includes compliance with the&#xD;
             requirements and restrictions listed in the informed consent form (ICF) and in this&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects are excluded from the study if any of the following criteria apply:&#xD;
&#xD;
        Medical Conditions&#xD;
&#xD;
          1. Subjects with resectable pancreatic cancer.&#xD;
&#xD;
          2. Evidence of metastatic disease.&#xD;
&#xD;
          3. Other malignancy that would interfere with the current intervention.&#xD;
&#xD;
          4. Any evidence of ascites (beyond trace).&#xD;
&#xD;
          5. Bulky celiac adenopathy (≥2.5 cm) or non-adenocarcinoma histology.&#xD;
&#xD;
          6. Previously treated malignancies, except for adequately treated non-melanoma skin&#xD;
             cancer, in situ cancer, or other cancers from which the subject has been disease-free&#xD;
             for at least 2 years.&#xD;
&#xD;
          7. History of clinically significant coagulopathy.&#xD;
&#xD;
          8. Major surgery, other than diagnostic surgery, within 4 weeks prior to study entry&#xD;
             without complete recovery.&#xD;
&#xD;
          9. New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial&#xD;
             infarction within 4 months prior to the first chemotherapy cycle Day 1, unstable&#xD;
             arrhythmia or symptomatic peripheral arterial vascular disease.&#xD;
&#xD;
         10. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic&#xD;
             therapy.&#xD;
&#xD;
         11. Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or&#xD;
             hepatitis C virus.&#xD;
&#xD;
         12. Females who are pregnant or breast-feeding.&#xD;
&#xD;
         13. Concomitant disease or condition that could interfere with the conduct of the study,&#xD;
             or that would, in the opinion of the Investigator, pose an unacceptable risk to the&#xD;
             subject in this study.&#xD;
&#xD;
             Prior/Concomitant Therapy&#xD;
&#xD;
         14. Any prior therapy for the treatment of pancreatic malignancy (including chemotherapy,&#xD;
             immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether&#xD;
             conventional or investigational).&#xD;
&#xD;
         15. Prior therapy with any hypoxic cytotoxic agent (hypoxia-targeting drugs).&#xD;
             Prior/Concurrent Clinical Study Experience&#xD;
&#xD;
         16. Subjects who are participating or participated in an investigational drug or device&#xD;
             study (within 28 days prior to study entry from the last study dose date).&#xD;
&#xD;
             Other Exclusions:&#xD;
&#xD;
         17. Unwillingness or inability to comply with the study protocol for any reason.&#xD;
&#xD;
         18. Known allergy to sesame oil.&#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>Eileen M O'Reilly, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Talia Golan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheba Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Orit Pollack-Shragai, MSc, MBA</last_name>
    <phone>+972-52-8466267</phone>
    <email>orit@silenseed.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hackensack Meridian Health</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Celina Ang, MD</last_name>
      <phone>212-824-8551</phone>
      <email>celina.ang@mssm.edu</email>
    </contact>
    <contact_backup>
      <last_name>Christopher DiMaio, MD</last_name>
      <phone>212-241-7531</phone>
      <email>christopher.dimaio@mountsinai.org</email>
    </contact_backup>
    <investigator>
      <last_name>Celina Ang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christopher J DiMaio, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eileen M O'Reilly, MD</last_name>
      <phone>646-888-4182</phone>
      <email>oreillye@mskcc.org</email>
    </contact>
    <contact_backup>
      <last_name>Anna M Varghese, MD</last_name>
      <phone>646-888-4308</phone>
      <email>VarghesA@mskcc.org</email>
    </contact_backup>
    <investigator>
      <last_name>Eileen M. O'Reilly, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anna M Varghese, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mark A Schattner, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Milind Javle, MD</last_name>
      <phone>713-792-5434</phone>
      <email>mjavle@mdanderson.org</email>
    </contact>
    <contact_backup>
      <last_name>Manoop Bhutani, MD</last_name>
      <phone>1-713-792-2121</phone>
      <email>Manoop.Bhutani@mdanderson.org</email>
    </contact_backup>
    <investigator>
      <last_name>Milind Javle, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Manoop Bhutani, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Center</name>
      <address>
        <city>Haifa</city>
        <zip>3525408</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Valerya Semenysty, MD</last_name>
      <phone>+972-4-7776419</phone>
      <email>semenysty@rambam.health.gov.il</email>
    </contact>
    <contact_backup>
      <last_name>Iyad Khamaysi, MD</last_name>
      <phone>+972-4-7773626</phone>
      <email>z_khamaysi@rambam.health.gov.ill</email>
    </contact_backup>
    <investigator>
      <last_name>Valerya Semenysty, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Iyad Khamaysi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petah Tikva</city>
        <zip>49102</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Sheba Medical Center (Tel H'shomer)</name>
      <address>
        <city>Ramat Gan</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Talia Golan, MD</last_name>
      <phone>+972-3-5305338</phone>
      <email>Talia.Golan@sheba.health.gov.il</email>
    </contact>
    <contact_backup>
      <last_name>Maor Lahav, MD</last_name>
      <phone>+972- 3-5305875</phone>
      <email>Maor.Lahav@sheba.health.gov.il</email>
    </contact_backup>
    <investigator>
      <last_name>Talia Golan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maor Lahav, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sourasky MC (Ichilov) Tel Aviv Israel</name>
      <address>
        <city>Tel Aviv</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ravit Geva, M.D</last_name>
      <phone>972- 36973082</phone>
      <email>ravitg@tlvmc.gov.il</email>
    </contact>
    <contact_backup>
      <last_name>Adam Phillips, M.D</last_name>
      <email>adamp@tlvmc.gov.il</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Assaf Harofeh Medical Center</name>
      <address>
        <city>Tzrifin</city>
        <zip>70300</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Israel</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.silenseed.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>June 30, 2021</last_update_submitted>
  <last_update_submitted_qc>June 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>siRNA</keyword>
  <keyword>RNA interference (RNAi)</keyword>
  <keyword>Cancer</keyword>
  <keyword>Pancreatic ductal adenocarcinoma</keyword>
  <keyword>Locally Advanced Pancreatic cancer</keyword>
  <keyword>Solid tumor</keyword>
  <keyword>Non operable pancreatic ductal adenocarcinoma</keyword>
  <keyword>Borderline resectable</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Pancreatic 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>Gemcitabine</mesh_term>
    <mesh_term>Folfirinox</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/NCT01676259
org study id: SLSG12D-P2
nct id: NCT01676259
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In this Phase II study a dose of 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered in
      12-week cycles to patients with unresectable or borderline resectable locally advanced
      pancreatic cancer combined with chemotherapy treatment.

      Primary Outcome:

      - ORR at 6 months.
In this Phase II study a dose of 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered in
      12-week cycles to patients with unresectable or borderline resectable LAPC combined with
      chemotherapy treatment (Gemcitabine+nab-Paclitaxel or Folfirinox or modified Folfirinox).
      This will be a study to assess the response rate of the siG12D-LODER in patients with
      unresectable or borderline resectable LAPC. The study is of a single arm design with one arm
      receiving siG12D-LODER + chemotherapy.

      The investigational agent siG12D-LODER is a miniature biodegradable bio polymeric matrix that
      encompasses the drug, designed and produced by Silenseed Ltd. The implantation of LODERs is
      selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures,
      proved to be highly effective and safe.

      siG12D-LODER has been studied in the escalating dose Phase I study of 15 patients, and
      results showed high safety and tolerability profiles, with no single DLT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: ORR at 6 months
time frame: One year
arm group label: siG12D-LODER + chemotherapy
arm group type: Experimental
description: Eight siG12D-LODER+Gemcitabine+nab-Paclitaxel or Eight siG12D-LODER+Folfirinox or Eight siG12D-LODER+modifide Folfirinox
intervention type: Drug
intervention name: siG12D-LODER
description: The implantation of siG12D-LODERs is selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures, proved to be highly effective and safe.
arm group label: siG12D-LODER + chemotherapy
intervention type: Drug
intervention name: Gemcitabine+nab-Paclitaxel
description: Gemcitabine+nab-Paclitaxel
arm group label: siG12D-LODER + chemotherapy
other name: Chemotherapy
intervention type: Drug
intervention name: Folfirinox
description: Folfirinox or modified Folfirinox
arm group label: siG12D-LODER + chemotherapy
other name: Chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eileen M O'Reilly, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
last name: Talia Golan, MD
role: Principal Investigator
affiliation: Sheba Medical Center
last name: Orit Pollack-Shragai, MSc, MBA
phone: +972-52-8466267
email: orit@silenseed.com
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Completed
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Active, not recruiting
country: Israel
country: United States
url: https://www.silenseed.com/
description: Related Info
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Pancreatic Neoplasms
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Folfirinox