Episcleral Topotecan for Treatment of Group D Retinoblastoma


This phase I trial will assess primarily the safety and secondarily the efficacy of Episcleral Topotecan in patients treated for Group D Retinoblastoma.

Full Title of Study: “A Phase I Study of Sequestered Transscleral, Controlled-Release Topotecan Delivered From An Episcleral Reservoir In Unilateral Group D Retinoblastoma Eyes”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 1, 2021

Detailed Description

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 feasibility and toxicity of topotecan delivered directly to the eye using a novel episcleral implant (also referred to as an episcleral reservoir). Children with newly diagnosed unilateral retinoblastoma classified as Group D according to the International Group Classification System will be eligible for the study if: (1) they have had no previous treatment, and (2) primary enucleation is a treatment recommendation. All enrolled eyes during a day-1 baseline EUA will be fitted with one or two episcleral implants (reservoirs) containing sustained release formulations of topotecan HCl as the only therapy for a four-week study period. Episcleral Topotecan will be supplied sterile and requires no manipulation other than placement on the eye. At a two-week EUA on day-15 of the four-week study period, if tumor response criteria are not met or if there is DLT, the Episcleral Reservoir will be removed and the patient will be off study and alternate interventions begun. In the event of enucleation remaining drug concentrations will be determined in the reservoir(s) as well as plasma concentration levels (anticipated to be below limits of detection based on preclinical studies). If tumor response criteria are met, the eye is eligible for continuing for the final two weeks of the study if there is no local, systemic or intraocular dose limiting toxicity (DLT) as defined in this protocol. At the end of the 4-week study period on study day-29 the third and final EUA will be conducted and tumor response and toxicity assessed. At that time, all reservoirs are removed and the eye is off study. Drug concentration/levels are determined in the removed reservoir(s), plasma, and tumor in the event of enucleation. The child and the eye shall then be treated at the discretion of the managing ophthalmologist and oncologist.


  • Drug: Episcleral Topotecan
    • Transscleral Topotecan

Arms, Groups and Cohorts

  • Experimental: Phase I Open Label Study
    • Phase I Single Arm

Clinical Trial Outcome Measures

Primary Measures

  • The primary outcome measure of the study is safety assessment as determined by comprehensive ophthalmic exam that enables determination of maximum tolerated dose.
    • Time Frame: 29 Days
    • The primary outcome measure of the study is safety assessment as determined by comprehensive ophthalmic exam that enables determination of maximum tolerated dose.

Secondary Measures

  • To determine systemic exposure by measurement of Topotecan in plasma.
    • Time Frame: 29 Days
    • To characterize the systemic exposure of episcleral topotecan by quantifying topotecan concentration in plasma.
  • To preliminarily define the antitumor activity as determine by reduction in maximal height of the tumor in the primary quadrant where the initial Episcleral Topotecan is placed.
    • Time Frame: 29 Days
    • To preliminarily define the antitumor activity as determine by reduction in maximal height of the tumor in the primary quadrant where the initial Episcleral Topotecan is placed.

Participating in This Clinical Trial

Inclusion Criteria

  • Age: Patients must be < 48 months of age and at least 12 months of age at the time the consent is signed by the parent(s) or guardian.
  • Diagnosis: Intraocular retinoblastoma, unilateral (Group D) in which enucleation is a recommended therapy.
  • Must have demonstrated intraocular calcium in the tumor containing eye by ophthalmic ultrasound or by neuroimaging.
  • Demonstration of Light Perception in the tumor-bearing eye either with pupil response testing or demonstration of avoidance behavior to light presentation in the affected eye
  • There must be no previous treatment for retinoblastoma or prior therapy with Episcleral Topotecan.
  • Performance Level: Lansky ³ 50.
  • Organ Function Requirements:

Organ function criteria:

1. Adequate Bone Marrow Function Defined as:

  • Peripheral absolute neutrophil count (ANC) ³ 1000/mm3
  • Platelet count ³ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Hemoglobin ³ 8.0 g/dL at baseline (may receive RBC transfusions)

2. Adequate Renal Function Defined as:

  • Creatinine clearance or radioisotope GFR ³70ml/min/1.73 m2 or
  • Adequate serum creatinine based on age/gender.
  • Adequate Liver Function Defined as:
  • Bilirubin (sum of conjugated + unconjugated) £ 1.5 x upper limit of normal (ULN) for age
  • SGPT (ALT) £ 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
  • Serum albumin ³ 2 g/dL.

Exclusion Criteria

  • Reported allergy to camptothecin, topotecan, or derivatives thereof.
  • Inability to comply with required study follow-up visits and stay within 50 miles of the treating institution during the first 15 days of study period (to EUA on Day 15).
  • Family history of retinoblastoma or retinoma.
  • Patients with International Stage retinoblastoma more advanced than Stage 0 and including:
  • Extra-ocular extension into orbit or brain, or
  • Metastatic retinoblastoma with or without CNS involvement, or
  • MRI showing thickening and enhancement of the optic nerve in either eye.

Gender Eligibility: All

Minimum Age: 12 Months

Maximum Age: 48 Months

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Targeted Therapy Technologies, LLC
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • David Carpi, MSc, 732-589-0934, dcarpi@3tophthalmics.com

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