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A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
This phase II trial tests the safety and side effects of adding melphalan (by injecting it into the eye) to standard chemotherapy in early treatment of patients with retinoblastoma (RB). RB is a type of cancer that forms in the tissues of the retina (the light-sensitive layers of nerve tissue at the back of the eye). It may be hereditary or nonhereditary (sporadic).
RB is considered harder to treat (higher risk) when there are vitreous seeds present. Vitreous seeds are RB tumors in the jelly-like fluid of the eye (called the vitreous humor). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment.
Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Other chemotherapy drugs given during this trial include carboplatin, vincristine, and etoposide.
Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells.
Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Etoposide is in a class of medications known as podophyllotoxin derivatives.
It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds and may be better than standard chemotherapy alone in treating retinoblastoma.
Study details:
PRIMARY OBJECTIVE:. I. To determine the feasibility of administering intravitreal melphalan by cycle 6 when given in combination with systemic carboplatin, vincristine, and etoposide (CVE) for the treatment of Group D retinoblastoma with vitreous seeding.
SECONDARY OBJECTIVES:. I. To determine the safety and toxicity profile associated with intravitreal melphalan in combination with systemic CVE for the treatment of Group D retinoblastoma with vitreous seeding.
II. To evaluate the efficacy of intravitreal melphalan in conjunction with systemic chemotherapy in Group D intraocular retinoblastoma with vitreous seeding. EXPLORATORY OBJECTIVES:.
I. To determine if eyes that become eligible for injection at cycle 3 or later would have been eligible for injection at diagnosis by retrospective central review of examination under anesthesia (EUA) and ultrasound biomicroscopy (UBM) images from diagnosis. II.
To validate and standardize the extraction, storage and collection protocols across multiple centers to demonstrate that aqueous humor from eyes undergoing therapy have high enough tumor-derived deoxyribonucleic acid (DNA) concentration for whole genome sequencing and RB1 testing. III. To explore the relationship between highly-recurrent retinoblastoma (RB) somatic copy number alterations (SCNAs) and ocular salvage as well as tumor fraction (% of tumor DNA) as a marker of minimal residual disease and risk of intraocular disease relapse.
IV. To evaluate the effects of intravitreal melphalan therapy in the histopathology of enucleated eyes for progressive or recalcitrant retinoblastoma while on therapy. V.
To evaluate the long-term visual potential of eyes salvaged using intravitreal therapy. OUTLINE:. CYCLES 1-2: Patients receive CVE regimen consisting of: carboplatin intravenously (IV) over 15-60 minutes on days 1 and 2 of each cycle, vincristine IV on day 1 of each cycle, and etoposide IV over 90-120 minutes on day 1 and 2 of each cycle.
Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ultrasound biomicroscopy (UBM) and imaging of the eye during a procedure called examination under anesthesia (EUA) at baseline and prior to each cycle. NOTE: UBM is completed prior to cycle 1 only.
CYCLES 3+: Patients receive CVE regimen as in cycles 1-2. Patients also undergo EUA prior to each cycle to determine eligibility to receive melphalan. If found eligible, patients receive intravitreal injection of melphalan once between days -14 to 14 of each cycle.
Patients who are not eligible for melphalan for any cycle receive CVE only regimen for that cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients may be eligible to receive additional cycles of melphalan alone (maximum of 6 injections).
Additionally, patients undergo magnetic resonance imaging and may undergo aqueous humor and tissue sample collection throughout the trial. After completion of study treatment, patients are followed up at 4 weeks, then every 3 months for 1 year, and then every 3-6 months for years 2-5.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 0 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2022-11-04
Primary completion: 2026-12-31
Study completion finish: 2026-12-31
Study type
TREATMENT
Phase
PHASE2
Trial ID
NCT05504291
Intervention or treatment
PROCEDURE: Biospecimen Collection
DRUG: Carboplatin
DRUG: Etoposide
PROCEDURE: Examination Under Anesthesia
PROCEDURE: Magnetic Resonance Imaging
DRUG: Melphalan
PROCEDURE: Ultrasound Biomicroscopy
DRUG: Vincristine
Conditions
- • Bilateral Retinoblastoma
- • Childhood Intraocular Retinoblastoma
- • Group D Retinoblastoma
- • Stage I Retinoblastoma
- • Unilateral Retinoblastoma
Find a site
Closest Location:
Perth Children's Hospital
Research sites nearby
Select from list below to view details:
Perth Children's Hospital
Perth, Western Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Treatment (CVE, melphalan)
| PROCEDURE: Biospecimen Collection
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Feasibility success rate of intravitreal melphalan injection in combination with systemic chemotherapy | A patient will be considered to have experienced intravitreal injection feasibility success if intravitreal melphalan can be delivered by cycle 6. If the treating physician does not inject because the eye has a full complete response (CR) for vitreous seeds after 2 cycles of systemic chemotherapy, it will be counted as a success in the feasibility analysis. Any feasibility evaluable patient who does not experience feasibility success will be considered a feasibility failure. For a bilateral patient with two Group D eyes with vitreous seeds, he/she will be categorized based on the worse results with the intent of being conservative, i.e., if intravitreal melphalan can be delivered in one eye but not the other by cycle 6 for any reason other than a CR of vitreal seeds, the patient will be deemed as experiencing a failure. | Up to cycle 6 (1 cycle = 28 days) |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Percentage of patients with grade 3 or higher toxicities | Any eligible patient who receives protocol therapy will be considered as evaluable for toxicity. | Up to 30 days after last dose of study treatment |
Event-free survival (EFS) | Any eligible patient who receives protocol therapy will be considered as evaluable for EFS. Patients who need non-protocol chemotherapy for either the study eye or non-study eye, external beam radiotherapy for either the study eye or non-study eye, or enucleation for the study eye will be considered as having a treatment failure and be considered as experiencing EFS events. The analysis will be conducted per patient level. The EFS along with the 95% confidence intervals will be estimated using the Kaplan-Meier method. | Up to 5 years |
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