RetinoblastomaPhase 1NCT04156347
Topotecan Episcleral Plaque for Treatment of Retinoblastoma
A Phase 1 study testing Episcleral Topotecan in people with Retinoblastoma, run by Targeted Therapy Technologies, LLC at 1 site in United States.
Trial summary
This single-arm, non-randomized, dose escalation phase I clinical trial will assess primarily the safety and secondarily the efficacy of episcleral topotecan in patients with active de novo or recurrent intraocular retinoblastoma in at least one eye following completion of first-line therapy. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Retinoblastoma
- What is being tested?
- Episcleral Topotecan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jun 2021to 14 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 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Participants must be < 21 years of age.
- Diagnosis and Treatment. Participants must have:
- Unilateral Group D or earlier-stage intraocular retinoblastoma in which enucleation is a recommended therapy, with no previous local or systemic therapy for retinoblastoma with intraocular calcium in the tumor-containing eye by ophthalmic ultrasound or neuroimaging.
- OR Active residual or recurrent intraocular retinoblastoma in at least one eye following completion of first-line therapy (focal therapy for IIRC Group A eyes, or systemic or intra-arterial chemotherapy).
- 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.
- Must have demonstrated intraocular calcium in the tumor-containing eye by ophthalmic ultrasound or by neuroimaging as part of standard retinoblastoma diagnosis.
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- Study eye must have vision potential, at least light perception vision in the tumor-bearing eye either with pupil response testing or demonstration of avoidance behavior to light presentation in the affected eye, and no clinical features suggestive of high risk of extraocular extension.
- Performance Level: Lansky greater than or equal 50 (<16 years of age); Karnofsky performance scale of >50 (>16 years of age).
- Organ Function Requirements:
- Adequate Bone Marrow Function defined as:
- Peripheral absolute neutrophil count (ANC) greater than or equal 1000/mm3
- Platelet count greater than or equal 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 Days prior to enrollment)
- Hemoglobin greater than or equal 8.0 g/dL at baseline (may receive RBC transfusions)
- Adequate Renal Function defined as:
- Creatinine clearance or radioisotope GFR greater than or equal 70ml/min/1.73 m2 or
- A serum creatinine based on age/gender as follows:
- Age Maximum Serum Creatinine (mg/dL) Male Female
- 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5
- to < 2 years 0.6 0.6
- to < 6 years 0.8 0.8
- 6 to < 7 years 1 1
- The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.
- Adequate Liver Function defined as:
- Bilirubin (sum of conjugated + unconjugated) less than or equal 1.5 x upper limit of normal (ULN) for age.
- SGPT (ALT) less than or equal 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
- Serum albumin greater than or requal 2 g/dL.
- 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 Episcleral Topotecan 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:
- tumor involving the optic nerve rim
- clinical or EUA evidence of extraocular extension
- evidence of metastatic retinoblastoma
- existing neuroimaging showing suspicion of, or definitive, optic nerve . invasion, trilateral retinoblastoma or extra-ocular extension.
- Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives thereof are excluded.
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- Concomitant treatment. Participants who have received chemotherapy, other focal retinoblastoma therapy or any other investigational agent within 3 weeks of Episcleral Topotecan placement are not eligible.
- 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, are not eligible.
- Febrile illness. Participants with clinically significant febrile illness (as determined by the investigator) within one week prior to initiation of protocol therapy are excluded.
- 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: A Phase I Study of Sequestered Transscleral, Controlled-Release Topotecan Delivered From an Episcleral Reservoir in Retinoblastoma Eyes
This single-arm, non-randomized, dose escalation phase I clinical trial will assess primarily the safety and secondarily the efficacy of episcleral topotecan in patients with active de novo 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 tumor 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 delivery system (also referred to as a Chemoplaque) in patients with active de novo 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
- Episcleral Topotecan
- Medical subject headings
- Retinoblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Episcleral TopotecanDrug
Also called Episcleral Topotecan, Transscleral Topotecan, Sustained Release Episcleral Topotecan, Chemoplaque
Transscleral Topotecan
| Study group | Role | What they receive |
|---|---|---|
| Phase I Open Label Study | Experimental | Phase I Single Arm Receives: Drug: Episcleral Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma-Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D).
To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma.
Measured: 9 Weeks
Secondary outcomes (2)
To determine systemic exposure by measurement of Topotecan in plasma.
To characterize the systemic exposure of episcleral topotecan by quantifying topotecan concentration in plasma.
Measured: 42 Days
To preliminarily define the antitumor activity as determine by assessments of tumor reponse;
To preliminarily define the antitumor activity as determine by assessment of tumor response.
Measured: 42 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2019
- Study start16 Jun 2021
- Primary completion1 Oct 2024 (estimated)
- Study completion14 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RetinoblastomaStudies of the same condition, open and under way.
- 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
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Targeted Therapy Technologies, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04156347
- Sponsor's protocol ID
- 3TRB01
- Status last verified
- Apr 2023
- First submitted
- 4 Nov 2019
- Last updated
- 31 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Sequestered Transscleral, Controlled-Release Topotecan Delivered From an Episcleral Reservoir in Retinoblastoma Eyes
- ClinicalTrials.gov ID
- NCT04156347
- Acronym / sponsor ID
- 3TRB01
- Conditions
- Retinoblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Targeted Therapy Technologies, LLCIndustry (pharma, biotech, devices)
- Study start
- 16 Jun 2021 (actual)
- Primary completion
- 1 Oct 2024 (estimated)
- Study completion
- 14 Oct 2024 (estimated)
- First posted
- 7 Nov 2019 (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-arm, non-randomized, dose escalation phase I clinical trial will assess primarily the safety and secondarily the efficacy of episcleral topotecan in patients with active de novo 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 tumor 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 delivery system (also referred to as a Chemoplaque) in patients with active de novo 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 Open Label Study | Experimental | Drug: Episcleral TopotecanPhase I Single Arm |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Age: Participants must be < 21 years of age.
- Unilateral Group D or earlier-stage intraocular retinoblastoma in which enucleation is a recommended therapy, with no previous local or systemic therapy for retinoblastoma with intraocular calcium in the tumor-containing eye by ophthalmic ultrasound or neuroimaging.
- OR Active residual or recurrent intraocular retinoblastoma in at least one eye following completion of first-line therapy (focal therapy for IIRC Group A eyes, or systemic or intra-arterial chemotherapy).
- 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.
- Must have demonstrated intraocular calcium in the tumor-containing eye by ophthalmic ultrasound or by neuroimaging as part of standard retinoblastoma diagnosis.
Key exclusion criteria (11 listed)
- tumor involving the optic nerve rim
- clinical or EUA evidence of extraocular extension
- evidence of metastatic retinoblastoma
- existing neuroimaging showing suspicion of, or definitive, optic nerve . invasion, trilateral retinoblastoma or extra-ocular extension.
- Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives thereof are excluded.
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 |
|---|---|---|
| Episcleral TopotecanAlso: Episcleral Topotecan, Transscleral Topotecan, Sustained Release Episcleral Topotecan, ChemoplaqueTransscleral Topotecan | Drug | Phase I Open Label Study |
Primary outcome
To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma-Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D).
Time frame: 9 Weeks
To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma.
2 secondary outcomes
To determine systemic exposure by measurement of Topotecan in plasma.
Time frame: 42 Days
To preliminarily define the antitumor activity as determine by assessments of tumor reponse;
Time frame: 42 Days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 Episcleral Topotecan in people with Retinoblastoma, run by Targeted Therapy Technologies, LLC at 1 site in United States.
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 28 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 31 Oct 2023. 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 United States. 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?
Results are not available in the source record.
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?
To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma-Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D). (time frame: 9 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2023.