RetinoblastomaPhase 1STEP-RBNCT04428879
Topotecan Episcleral Plaque for Treatment of Retinoblastoma
A Phase 1 study testing Topotecan Episcleral Plaque in people with Retinoblastoma, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
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 de novo or residual or recurrent intraocular retinoblastoma in at least one eye following completion of first-line… Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Retinoblastoma
- What is being tested?
- Topotecan Episcleral Plaque
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteCanada
- Study dates
- 16 Jun 2020to 3 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age. Participants must be <18 years of age.
- Diagnosis and Treatment. Participants must have: (i) active residual or recurrent intraocular retinoblastoma following completion of first-line therapy (chemotherapy, systemic or intra-arterial, focal therapy or brachytherapy), or (ii) unilateral Group B, C, D or cT1b, cT2 retinoblastoma at diagnosis with no previous treatment.
- One eye will be the Study Eye. When participants 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.
- Disease status. Study eye must have vision potential and no clinical features suggestive of high risk of extraocular extension.
- Performance status. Lansky play score ≥ 50 if <16 years of age; Karnofsky performance scale of ≥ 50 if ≥16 years of age (Appendix I)
- Organ function:
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- Adequate bone marrow function and platelet count
- Adequate renal function
- Adequate liver function
- 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
- Informed consent. All participants 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.
Who cannot join
- Disease status. Participants known to have any of the following are excluded:
- clinical or EUA evidence of extraocular extension
- known metastatic disease status and intercurrent illness
- existing clinical and neuroimaging showing suspicion of, or definitive,
- Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives thereof.
- Concomitant treatment. Participants 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.
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- Uncontrolled intercurrent illness. Participants with known uncontrolled intercurrent illness that, in the investigator's opinion, would put the participant at undue risk or limit compliance with the study requirements.
- Febrile illness. Participants with clinically significant febrile illness (as determined by the investigator) within one week prior to initiation of protocol therapy.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Sustained-Release Topotecan Episcleral Plaque (Chemoplaque) for Retinoblastoma
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 de novo or residual or recurrent intraocular retinoblastoma in at least one eye following completion of first-line therapy.
Read the 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.
- Conditions
- Retinoblastoma
- Being tested
- Topotecan Episcleral Plaque
- Keywords
- Retinal Neoplasms, Neoplasms, Eye Neoplasms, Eye Diseases, Hereditary, Eye Diseases, Retinal Diseases, Topotecan
- Medical subject headings
- Retinoblastoma, Retinal Neoplasms, Neoplasms, Eye Neoplasms, Eye Diseases, Hereditary, Eye Diseases, Retinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topotecan Episcleral PlaqueDrug
Also called Episcleral Topotecan, Transscleral Topotecan, Sustained Release Episcleral Topotecan, Chemoplaque
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).
| Study group | Role | What they receive |
|---|---|---|
| Phase I single arm trial | Experimental | Not described Receives: Drug: Topotecan Episcleral Plaque |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose and Recommended Phase 2 Dose of topotecan hydrochloride administered as a Chemoplaque to pediatric patients with active Retinoblastoma.
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).
Measured: 9 weeks
Secondary outcomes (1)
Tumor response to the Chemoplaque as secondary therapy in eye(s) with active retinoblastoma after completion of primary standard of care treatment.
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.
Measured: 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start16 Jun 2020
- Primary completion1 Oct 2024
- Study completion3 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for RetinoblastomaStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brenda Gallie, The Hospital for Sick Children
- Investigators
- Brenda Gallie, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04428879
- Sponsor's protocol ID
- 1000064742
- Acronym
- STEP-RB
- Status last verified
- Oct 2024
- First submitted
- 4 Jun 2020
- Last updated
- 13 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gallie BL, Flegg K, Truong T, Liu J, Gavrylyuk Y, Chau K, Kletke S, Malliipatna A, Sheikh F, Soroka S, Ozkurt ZG, Alshahran N, Jong A, Janusonis I. Digital retinoblastoma documentation supports care and research. Can J Ophthalmol. 2025 Apr;60(2):100-106. doi: 10.1016/j.jcjo.2024.06.007. Epub 2024 Jul 31.
PubMed 39095033
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Sustained-Release Topotecan Episcleral Plaque (Chemoplaque) for Retinoblastoma
- ClinicalTrials.gov ID
- NCT04428879
- Acronym / sponsor ID
- STEP-RB / 1000064742
- Conditions
- Retinoblastoma
- Keywords
- Retinal Neoplasms, Neoplasms, Eye Neoplasms, Eye Diseases, Hereditary, Eye Diseases, Retinal Diseases, Topotecan
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- 16 Jun 2020 (actual)
- Primary completion
- 1 Oct 2024 (actual)
- Study completion
- 3 Oct 2024 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 de novo or 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I single arm trial | Experimental | Drug: Topotecan Episcleral Plaque |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Age. Participants must be <18 years of age.
- Diagnosis and Treatment. Participants must have: (i) active residual or recurrent intraocular retinoblastoma following completion of first-line therapy (chemotherapy, systemic or intra-arterial, focal therapy or brachytherapy), or (ii) unilateral Group B, C, D or cT1b, cT2 retinoblastoma at diagnosis with no previous treatment.
- One eye will be the Study Eye. When participants 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.
- Disease status. Study eye must have vision potential and no clinical features suggestive of high risk of extraocular extension.
- Performance status. Lansky play score ≥ 50 if <16 years of age; Karnofsky performance scale of ≥ 50 if ≥16 years of age (Appendix I)
Key exclusion criteria (10 listed)
- Disease status. Participants known to have any of the following are excluded:
- Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives thereof.
- Concomitant treatment. Participants 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.
- Uncontrolled intercurrent illness. Participants with known uncontrolled intercurrent illness that, in the investigator's opinion, would put the participant at undue risk or limit compliance with the study requirements.
- Febrile illness. Participants with clinically significant febrile illness (as determined by the investigator) within one week prior to initiation of protocol therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topotecan Episcleral PlaqueAlso: Episcleral Topotecan, Transscleral Topotecan, Sustained Release Episcleral Topotecan, ChemoplaqueSustained 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). | Drug | Phase I single arm trial |
Primary outcome
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
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).
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
- Derived from this study: PubMed 39095033Gallie BL, Flegg K, Truong T, Liu J, Gavrylyuk Y, Chau K, Kletke S, Malliipatna A, Sheikh F, Soroka S, Ozkurt ZG, Alshahran N, Jong A, Janusonis I. Digital retinoblastoma documentation supports care and research. Can J Ophthalmol. 2025 Apr;60(2):100-106. doi: 10.1016/j.jcjo.2024.06.007. Epub 2024 Jul 31.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brenda Gallie principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Topotecan Episcleral Plaque in people with Retinoblastoma, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04428879, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2024.