<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/NCT04428879</url>
  </required_header>
  <id_info>
    <org_study_id>1000064742</org_study_id>
    <nct_id>NCT04428879</nct_id>
  </id_info>
  <brief_title>Topotecan Episcleral Plaque for Treatment of Retinoblastoma</brief_title>
  <acronym>STEP-RB</acronym>
  <official_title>Phase I Sustained-Release Topotecan Episcleral Plaque (Chemoplaque) for Retinoblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Hospital for Sick Children</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This single site, single-arm, non-randomized, dose escalation phase I toxicity clinical trial&#xD;
      will assess primarily the safety and secondarily the efficacy of episcleral topotecan in&#xD;
      patients with active residual or recurrent intraocular retinoblastoma in at least one eye&#xD;
      following completion of first-line therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Retinoblastoma is the most common pediatric malignant intraocular tumour and originates from&#xD;
      the retina. Treatment of eyes with advanced intraocular retinoblastoma remains a challenge.&#xD;
      The historic standard of care for patients with unilateral disease is enucleation and for&#xD;
      those with bilateral disease, a variety of modalities have been tried. These include&#xD;
      radiation therapy, systemic chemotherapy, periocular administration of chemotherapy,&#xD;
      selective intra-arterial chemotherapy, and intravitreal chemotherapy. Unfortunately, all of&#xD;
      these modalities are associated with significant morbidity and investigators are looking for&#xD;
      new ways to treat these patients either with novel directed drug delivery methods or with new&#xD;
      less toxic agents. This study will evaluate the safety and efficacy of topotecan delivered&#xD;
      directly to the eye using a novel sustained-release topotecan episcleral plaque (also&#xD;
      referred to as a Chemoplaque) in patients with active residual or recurrent intraocular&#xD;
      retinoblastoma in at least one eye following completion of first-line therapy. The study&#xD;
      intervention involves the insertion and removal of the Chemoplaque, examinations under&#xD;
      anaesthesia (EUAs), visits to clinic to monitor for adverse events throughout, and post&#xD;
      plaque removal toxicity evaluation. EUAs, clinic visits and laboratory tests are standard of&#xD;
      care for retinoblastoma patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 16, 2020</start_date>
  <completion_date type="Anticipated">October 15, 2030</completion_date>
  <primary_completion_date type="Anticipated">October 15, 2025</primary_completion_date>
  <phase>Phase 1</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>Maximum Tolerated Dose and Recommended Phase 2 Dose of topotecan hydrochloride administered as a Chemoplaque to pediatric patients with active Retinoblastoma.</measure>
    <time_frame>9 weeks</time_frame>
    <description>Inter-Patient Escalation in the rolling six phase 1 trial design will determine Maximum Tolerated Dose and Recommended Phase 2 Dose. Dose level assignment is based on the number of participants currently enrolled in the cohort, the number of dose limiting toxicities observed, and the number of participants at risk for developing a dose limiting toxicity (i.e., participants enrolled but who are not yet assessable for toxicity).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor response to the Chemoplaque as secondary therapy in eye(s) with active retinoblastoma after completion of primary standard of care treatment.</measure>
    <time_frame>9 weeks</time_frame>
    <description>Tumor response will be characterized as (i) complete regression, (ii) very good (iii) partial regression, (iv) partial regression, (v) stable disease or (vi) progressive disease determined by evaluating number of tumour sites, appearance and tumour size.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Retinoblastoma</condition>
  <arm_group>
    <arm_group_label>Phase I single arm trial</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topotecan Episcleral Plaque</intervention_name>
    <description>Sustained Release Episcleral Topotecan Plaques (Chemoplaques) are glued to bare, dry sclera of the eye under conjunctiva and Tenon's capsule. A rolling six dose interpatient escalation schema will be employed. Chemoplaques with 0.6 mg and 0.9 mg of topotecan HCl formulation are available. Patients will receive 1 or 2 Chemoplaques per eye, to deliver 5 escalating doses: 0.6, 0.9, 1.2 [2x0.6], 1.5 [0.6+0.9] or 1.8 [2x0.9] mg. The prescribed dose will escalate or de-escalate by 0.3 mg at each level, and no patient will receive more than 1.8 mg of topotecan hydrochloride due to the physical limitations if the devices available. The planned removal is 42 days ± 7, unless dose limiting toxicity is observed, in which case the plaque is removed as soon as possible. The observation period for the purposes of dose-escalation will be 63 days (i.e. 21 days following Chemoplaque removal on day 42).</description>
    <arm_group_label>Phase I single arm trial</arm_group_label>
    <other_name>Episcleral Topotecan</other_name>
    <other_name>Transscleral Topotecan</other_name>
    <other_name>Sustained Release Episcleral Topotecan</other_name>
    <other_name>Chemoplaque</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age. Participants must be &lt;18 years of age.&#xD;
&#xD;
          2. Diagnosis and Treatment. Participants must have: (i) active residual or recurrent&#xD;
             intraocular retinoblastoma following completion of first-line therapy (chemotherapy,&#xD;
             systemic or intra-arterial, focal therapy or brachytherapy), or (ii) unilateral Group&#xD;
             B, C, D or cT1b, cT2 retinoblastoma at diagnosis with no previous treatment.&#xD;
&#xD;
          3. One eye will be the Study Eye. When participants have two eyes with retinoblastoma,&#xD;
             the eye with worst disease or best vision potential will be designated the Study Eye.&#xD;
             There will only be one eye per child treated in this Phase I study, since treatment of&#xD;
             two eyes would double the systemic dose of drug. The Non-study eye will be treated by&#xD;
             standard of care, with only focal therapy during the Study Period, if required.&#xD;
&#xD;
          4. Disease status. Study eye must have vision potential and no clinical features&#xD;
             suggestive of high risk of extraocular extension.&#xD;
&#xD;
          5. Performance status. Lansky play score ≥ 50 if &lt;16 years of age; Karnofsky performance&#xD;
             scale of ≥ 50 if ≥16 years of age (Appendix I)&#xD;
&#xD;
          6. Organ function:&#xD;
&#xD;
               1. Adequate bone marrow function and platelet count&#xD;
&#xD;
               2. Adequate renal function&#xD;
&#xD;
               3. Adequate liver function&#xD;
&#xD;
          7. Pregnancy prevention. Females of reproductive potential must agree to the use of&#xD;
             highly effective contraception during study participation and for an additional 40&#xD;
             days after the end of the Chemoplaque administration&#xD;
&#xD;
          8. Informed consent. All participants and/or their parents or legally authorized&#xD;
             representatives must have the ability to understand and the willingness to sign a&#xD;
             written informed consent. Assent, where appropriate, will also be obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Disease status. Participants known to have any of the following are excluded:&#xD;
&#xD;
               1. clinical or EUA evidence of extraocular extension&#xD;
&#xD;
               2. known metastatic disease status and intercurrent illness&#xD;
&#xD;
               3. existing clinical and neuroimaging showing suspicion of, or definitive,&#xD;
&#xD;
          2. Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives&#xD;
             thereof.&#xD;
&#xD;
          3. Concomitant treatment. Participants may not receive chemotherapy or other focal&#xD;
             retinoblastoma therapy or any other investigational agent within 3 weeks of the&#xD;
             placement and removal of the Chemoplaque, nor while the Chemoplaque is in situ.&#xD;
&#xD;
          4. Uncontrolled intercurrent illness. Participants with known uncontrolled intercurrent&#xD;
             illness that, in the investigator's opinion, would put the participant at undue risk&#xD;
             or limit compliance with the study requirements.&#xD;
&#xD;
          5. Febrile illness. Participants with clinically significant febrile illness (as&#xD;
             determined by the investigator) within one week prior to initiation of protocol&#xD;
             therapy.&#xD;
&#xD;
          6. Pregnancy and lactation. Females of reproductive potential must have a negative serum&#xD;
             pregnancy test within 72 hours prior to initiation of protocol therapy. Due to the&#xD;
             unknown but potential risk for adverse events (AEs) in nursing infants secondary to&#xD;
             treatment of the mother with the study agents, breastfeeding must be discontinued if&#xD;
             the mother is treated on study.&#xD;
&#xD;
          7. Compliance. Any condition of diagnosis that could in the opinion of the Principal&#xD;
             Investigator or delegate interfere with the participant's ability to comply with the&#xD;
             study instruction, might confound the interpretation of the study results, or put the&#xD;
             participant at risk.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brenda Gallie</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Hospital for Sick Children</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kaitlyn Flegg</last_name>
    <phone>416-813-7654</phone>
    <phone_ext>203297</phone_ext>
    <email>kaitlyn.flegg@sickkids.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Aiman Siddiqi</last_name>
    <phone>416-813-7654</phone>
    <phone_ext>228928</phone_ext>
    <email>aiman.siddiqi@sickkids.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brenda Gallie, MD, FRCSC</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>May 18, 2021</last_update_submitted>
  <last_update_submitted_qc>May 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Hospital for Sick Children</investigator_affiliation>
    <investigator_full_name>Brenda Gallie</investigator_full_name>
    <investigator_title>Head, Retinoblastoma Program</investigator_title>
  </responsible_party>
  <keyword>Retinal Neoplasms</keyword>
  <keyword>Neoplasms</keyword>
  <keyword>Eye Neoplasms</keyword>
  <keyword>Eye Diseases, Hereditary</keyword>
  <keyword>Eye Diseases</keyword>
  <keyword>Retinal Diseases</keyword>
  <keyword>Topotecan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinoblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Topotecan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04428879
org study id: 1000064742
nct id: NCT04428879
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This single site, single-arm, non-randomized, dose escalation phase I toxicity clinical trial
      will assess primarily the safety and secondarily the efficacy of episcleral topotecan in
      patients with active residual or recurrent intraocular retinoblastoma in at least one eye
      following completion of first-line therapy.
Retinoblastoma is the most common pediatric malignant intraocular tumour and originates from
      the retina. Treatment of eyes with advanced intraocular retinoblastoma remains a challenge.
      The historic standard of care for patients with unilateral disease is enucleation and for
      those with bilateral disease, a variety of modalities have been tried. These include
      radiation therapy, systemic chemotherapy, periocular administration of chemotherapy,
      selective intra-arterial chemotherapy, and intravitreal chemotherapy. Unfortunately, all of
      these modalities are associated with significant morbidity and investigators are looking for
      new ways to treat these patients either with novel directed drug delivery methods or with new
      less toxic agents. This study will evaluate the safety and efficacy of topotecan delivered
      directly to the eye using a novel sustained-release topotecan episcleral plaque (also
      referred to as a Chemoplaque) in patients with active residual or recurrent intraocular
      retinoblastoma in at least one eye following completion of first-line therapy. The study
      intervention involves the insertion and removal of the Chemoplaque, examinations under
      anaesthesia (EUAs), visits to clinic to monitor for adverse events throughout, and post
      plaque removal toxicity evaluation. EUAs, clinic visits and laboratory tests are standard of
      care for retinoblastoma patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose and Recommended Phase 2 Dose of topotecan hydrochloride administered as a Chemoplaque to pediatric patients with active Retinoblastoma.
time frame: 9 weeks
description: Inter-Patient Escalation in the rolling six phase 1 trial design will determine Maximum Tolerated Dose and Recommended Phase 2 Dose. Dose level assignment is based on the number of participants currently enrolled in the cohort, the number of dose limiting toxicities observed, and the number of participants at risk for developing a dose limiting toxicity (i.e., participants enrolled but who are not yet assessable for toxicity).
measure: Tumor response to the Chemoplaque as secondary therapy in eye(s) with active retinoblastoma after completion of primary standard of care treatment.
time frame: 9 weeks
description: Tumor response will be characterized as (i) complete regression, (ii) very good (iii) partial regression, (iv) partial regression, (v) stable disease or (vi) progressive disease determined by evaluating number of tumour sites, appearance and tumour size.
arm group label: Phase I single arm trial
arm group type: Experimental
intervention type: Drug
intervention name: Topotecan Episcleral Plaque
description: Sustained Release Episcleral Topotecan Plaques (Chemoplaques) are glued to bare, dry sclera of the eye under conjunctiva and Tenon's capsule. A rolling six dose interpatient escalation schema will be employed. Chemoplaques with 0.6 mg and 0.9 mg of topotecan HCl formulation are available. Patients will receive 1 or 2 Chemoplaques per eye, to deliver 5 escalating doses: 0.6, 0.9, 1.2 [2x0.6], 1.5 [0.6+0.9] or 1.8 [2x0.9] mg. The prescribed dose will escalate or de-escalate by 0.3 mg at each level, and no patient will receive more than 1.8 mg of topotecan hydrochloride due to the physical limitations if the devices available. The planned removal is 42 days ± 7, unless dose limiting toxicity is observed, in which case the plaque is removed as soon as possible. The observation period for the purposes of dose-escalation will be 63 days (i.e. 21 days following Chemoplaque removal on day 42).
arm group label: Phase I single arm trial
other name: Episcleral Topotecan
other name: Transscleral Topotecan
other name: Sustained Release Episcleral Topotecan
other name: Chemoplaque
criteria: 
gender: All
minimum age: N/A
maximum age: 17 Years
healthy volunteers: No
last name: Brenda Gallie
role: Principal Investigator
affiliation: The Hospital for Sick Children
last name: Kaitlyn Flegg
phone: 416-813-7654
phone ext: 203297
email: kaitlyn.flegg@sickkids.ca
last name: Aiman Siddiqi
phone: 416-813-7654
phone ext: 228928
email: aiman.siddiqi@sickkids.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: The Hospital for Sick Children
investigator full name: Brenda Gallie
investigator title: Head, Retinoblastoma Program
mesh term: Retinoblastoma
mesh term: Topotecan
sharing ipd: No