Topotecan Episcleral Plaque for Treatment of Retinoblastoma

NCT ID: NCT04428879

Last Updated: 2024-12-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-16
• Study Completion Date: 2024-10-03

Brief 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 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.

Conditions

Retinoblastoma

Keywords

Retinal Neoplasms; Neoplasms; Eye Neoplasms; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Topotecan

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I single arm trial

Group Type: EXPERIMENTAL

Topotecan Episcleral Plaque

Intervention Type: DRUG

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).

Interventions

Topotecan Episcleral Plaque

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).

Intervention Type: DRUG

Other Intervention Names

Episcleral Topotecan; Transscleral Topotecan; Sustained Release Episcleral Topotecan; Chemoplaque

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
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Brenda Gallie

Head, Retinoblastoma Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brenda Gallie

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

1000064742

Identifier Type: -

Identifier Source: org_study_id