Clinical Trials /

Topotecan Episcleral Plaque for Treatment of Retinoblastoma

NCT04428879

Description:

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.

Related Conditions:
  • Intraocular Retinoblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Topotecan Episcleral Plaque for Treatment of Retinoblastoma
  • Official Title: Phase I Sustained-Release Topotecan Episcleral Plaque (Chemoplaque) for Retinoblastoma

Clinical Trial IDs

  • ORG STUDY ID: 1000064742
  • NCT ID: NCT04428879

Conditions

  • Retinoblastoma

Interventions

DrugSynonymsArms
Topotecan Episcleral PlaqueEpiscleral Topotecan, Transscleral Topotecan, Sustained Release Episcleral Topotecan, ChemoplaquePhase I single arm trial

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase I single arm trialExperimental
  • Topotecan Episcleral Plaque

Eligibility Criteria

        Inclusion Criteria:

          1. Age. Patients must be <18 years of age.

          2. Diagnosis and Treatment. Patients must have active residual or recurrent intraocular
             retinoblastoma in at least one eye following completion of first-line therapy
             (chemotherapy, systemic or intra-arterial, or brachytherapy).

          3. One eye will be the Study Eye. When patients have two eyes with retinoblastoma, the
             eye with worst disease or best vision potential will be designated the Study Eye.
             There will only be one eye per child treated in this Phase I study, since treatment of
             two eyes would double the systemic dose of drug. The Non-study eye will be treated by
             standard of care, with only focal therapy during the Study Period, if required.

          4. Disease status. Study eye must have vision potential and no clinical features
             suggestive of high risk of extraocular extension.

          5. Performance status. Lansky play score ≥ 50 if <16 years of age; Karnofsky performance
             scale of ≥ 50 if ≥16 years of age (Appendix I)

          6. Organ function:

               1. Adequate bone marrow function and platelet count

               2. Adequate renal function

               3. Adequate liver function

          7. Pregnancy prevention. Females of reproductive potential must agree to the use of
             highly effective contraception during study participation and for an additional 40
             days after the end of the Chemoplaque administration

          8. Informed consent. All patients and/or their parents or legally authorized
             representatives must have the ability to understand and the willingness to sign a
             written informed consent. Assent, where appropriate, will also be obtained.

        Exclusion Criteria:

          1. Disease status. Any of the following:

               1. tumour involving the optic nerve rim

               2. clinical or EUA evidence of extraocular extension

               3. evidence of metastatic retinoblastoma

               4. existing neuroimaging showing suspicion of, or definitive, optic nerve invasion,
                  trilateral retinoblastoma or extra-ocular extension.

          2. Allergy. Reported allergy to topotecan, camptothecin or derivatives thereof.

          3. Concomitant treatment. Patients may not receive chemotherapy or other focal
             retinoblastoma therapy or any other investigational agent within 3 weeks of the
             placement and removal of the Chemoplaque, nor while the Chemoplaque is in situ.

          4. Uncontrolled intercurrent illness. Patients with uncontrolled intercurrent illness
             that, in the investigator's opinion, would put the participant at undue risk or limit
             compliance with the study requirements.

          5. Febrile illness. Patients with clinically significant febrile illness (as determined
             by the investigator) within one week prior to initiation of protocol therapy.

          6. Pregnancy and lactation. Females of reproductive potential must have a negative serum
             pregnancy test within 72 hours prior to initiation of protocol therapy. Due to the
             unknown but potential risk for adverse events (AEs) in nursing infants secondary to
             treatment of the mother with the study agents, breastfeeding must be discontinued if
             the mother is treated on study.

          7. Compliance. Any condition of diagnosis that could in the opinion of the Principal
             Investigator or delegate interfere with the participant's ability to comply with the
             study instruction, might confound the interpretation of the study results, or put the
             participant at risk.
      
Maximum Eligible Age:17 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
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).

Secondary Outcome Measures

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
Safety Issue:
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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Hospital for Sick Children

Trial Keywords

  • Retinal Neoplasms
  • Neoplasms
  • Eye Neoplasms
  • Eye Diseases, Hereditary
  • Eye Diseases
  • Retinal Diseases
  • Topotecan

Last Updated

June 23, 2020