# Phase I Clinical Investigation of Episcleral Topotecan in Retinoblastoma

> **NIH FDA R01** · TARGETED THERAPY TECHNOLOGIES, LLC · 2021 · $220,000

## Abstract

Abstract
Retinoblastoma (RB) is a rare (micro-orphan disease) intraocular cancer in infants and children (typically
diagnosed between birth and 5 years of age). See FDA OOPD orphan drug letter designation for RB in
Appendix documents. Approximately, 250 new cases are diagnosed annually in the United States.
Current standard treatment of affected children consists of either removing the one affected eye (in the
case of unilateral disease), or by giving systemic chemotherapy for a period of 6-9 months, or by giving
multiple regional (intra-arterial) chemotherapy (IAC) infusions. Systemic chemotherapy is associated
with bone-marrow toxicity and relatively high costs. External beam radiotherapy is no longer standard
primary therapy. There has never been an FDA approved intervention for Rb.
Episcleral Topotecan (IND #112785) is a novel system for making possible the sustained local delivery
of Topotecan directly to the interior of the eye without breaching the eye wall (by injection or incision)
while sequestering Topotecan from washout to peripheral circulation. Local Episcleral Topotecan may
reduce or eliminate the need for systemic chemotherapy. Inside the impermeable silicone episcleral
device, the contents of the drug reservoir are maintained in direct contact with a broad expanse of the
outer surface of the eye wall (the episclera), greatly facilitating the net passive unidirectional transscleral
diffusion of the drug to the intraocular tumor inside the eye. Episcleral Topotecan enables sustained-
release delivery of Topotecan with continuous-high-dose Topotecan retinal delivery while eliminating
detectable system exposure and systemic toxicity.
This FDA Orphan Drug Grant application requests funding to support Phase I clinical trials in patients
with advanced unilateral group D retinoblastoma at presentation. In developing countries as many as half
of all children diagnosed with retinoblastoma care are abandoned by the family for cultural or social
reasons (Kumar, A., et al. (2013). "Causes, outcome and prevention of abandonment in retinoblastoma in
India—Pediatr Blood Cancer 60(5): 771-775). Current options for the primary treatment of RB children
include, enucleation, systemic chemotherapy, and IAC. These therapeutic options are invasive, costly
and associated with significant side effects. Episcleral Topotecan offers a potential therapeutic avenue
that is less invasive and less costly with far fewer side effects. It also could be the first FDA-approved
therapy for this micro-orphan childhood disease.
Under Emergency Use protocol, we've treated our first RB patient. This child had failed multiple cycles
of systemic chemo and IAC. The child had >10 refractory tumors and vitreous seeds in his remaining
eye. Post Episcleral Topotecan placement, all tumors and vitreous seeds were resolved by day 28 and all
but two tumors were resolved by day 12. As of day 98 EUA, there was no recurrence. There was no
systemic toxicity and there was no ocular toxi...

## Key facts

- **NIH application ID:** 9989088
- **Project number:** 5R01FD005388-02
- **Recipient organization:** TARGETED THERAPY TECHNOLOGIES, LLC
- **Principal Investigator:** Ricardo A Carvalho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $220,000
- **Award type:** 5
- **Project period:** 2019-08-05 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989088

## Citation

> US National Institutes of Health, RePORTER application 9989088, Phase I Clinical Investigation of Episcleral Topotecan in Retinoblastoma (5R01FD005388-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989088. Licensed CC0.

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