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.
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
Interventions
Drug | Synonyms | Arms |
---|
Topotecan Episcleral Plaque | Episcleral Topotecan, Transscleral Topotecan, Sustained Release Episcleral Topotecan, Chemoplaque | Phase 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
Name | Type | Description | Interventions |
---|
Phase I single arm trial | Experimental | | - Topotecan Episcleral Plaque
|
Eligibility Criteria
Inclusion Criteria:
1. Age. Participants must be <18 years of age.
2. 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.
3. 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.
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 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.
Exclusion Criteria:
1. Disease status. Participants known to have any of the following are excluded:
1. clinical or EUA evidence of extraocular extension
2. known metastatic disease status and intercurrent illness
3. existing clinical and neuroimaging showing suspicion of, or definitive,
2. Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives
thereof.
3. 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.
4. 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.
5. Febrile illness. Participants 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
May 20, 2021